Critical Care
The Southwest Journal of Pulmonary and Critical Care publishes articles directed to those who treat patients in the ICU, CCU and SICU including chest physicians, surgeons, pediatricians, pharmacists/pharmacologists, anesthesiologists, critical care nurses, and other healthcare professionals. Manuscripts may be either basic or clinical original investigations or review articles. Potential authors of review articles are encouraged to contact the editors before submission, however, unsolicited review articles will be considered.
Loperamide Abuse: A Case Report and Brief Review
Jaclyn Leong DO1
Kava Afu MS-32
Ella Starobinska MD1
Michael Insel MD3
1Department of Internal Medicine, 2University of Arizona College of Medicine, and 3Department of Pulmonary and Critical Care
Banner University Medical Center
Tucson, AZ USA
Case Presentation
A 29-year-old man with unspecified mood disorder, childhood attention deficit hyperactivity disorder, and 2 prior suicide attempts with zolpidem and methadone presented with altered mental status as a transfer from an outside hospital. The patient was found in his truck outside of a grocery store by a bystander who contacted emergency medical services. At the time, he was noted to have seizure-like activity. He had an empty shopping bag in his possession with 14 empty loperamide (Imodium®) bottles, each were supposed to contain 24 tablets. The patient was taken to the nearest medical facility where he was found to be in status epilepticus. After no response to 4 mg intravenous (IV) lorazepam, he was then intubated for airway protection. Propofol infusion was started and a loading dose of levetiracetam 1600 mg IV was administered. Despite medical management, he continued to show evidence of seizure-like activity. Due to the lack of a neurology service at the hospital, the patient was transferred to our academic medical center.
On arrival, patient was intubated, sedated and hemodynamically stable. Sedation was paused to allow a thorough neurologic examination, at which time, he became agitated and was not redirectable. However, he did not exhibit seizure activity. Toxicology service was consulted for suspected loperamide overdose.
Laboratory workup revealed white blood cell count 16,600 µL with neutrophilic predominance (4000-11000), glucose 205 (70- 106 mg/dL), lactic acid of 10 (0.5- 1.7 mmol/L), creatinine kinase 164 (35- 232 IU/L), creatinine 1.39 ( 0.60- 1.50 mg/dL), EGFR 79 (Normal Low >=60). Tylenol and salicylate levels were undetectable. Urine drug screen was negative. Computer tomography (CT) of the head showed no acute intracranial process. CT abdomen/pelvis showed bibasilar airspace consolidations concerning for aspiration pneumonia. Echo revealed left ventricular ejection fraction of 38% with a large-sized apical, septal, anteroseptal, anterior, inferior, posterior, and lateral wall motion abnormality with hypokinesis to akinesis of the segments.
Electrocardiograms (ECG) initially showed QTc and QRS prolongation of 571 ms and 160 ms, respectively. During the initial 24-hours at our hospital, serial EKGs were performed to monitor QTc. Additionally, patient was treated empirically for aspiration pneumonia with ampicillin/sulbactam.
On day two of his hospitalization, his ECG revealed sinus rhythm, with first-degree AV block and QT prolongation greater than 700 ms. Subsequently, torsades de pointes developed, progressing into ventricular tachycardia storm. Several ampules of bicarbonate were administered, and the patient was cardioverted. Dobutamine and magnesium infusions were started and a temporary transvenous pacer was placed with overdrive pacing initiated at 110 bpm. Over the next 24 hours, magnesium and dobutamine were discontinued. The transvenous pacer was removed on hospital day 4 after the patient demonstrated a native rhythm with normal QRS and QT intervals. Levetiracetam was also discontinued, per neurology recommendations. The patient was safely extubated on hospital day 5. He was subsequently evaluated by the psychiatry service who scheduled close follow up after discharge.
Discussion
Loperamide is a nonprescription drug used most commonly to control acute, nonspecific diarrhea, as well as chronic diarrhea associated with inflammatory bowel disease. It acts on mu-opioid receptors in the myenteric plexus to reduce peristaltic activity, thus lengthening bowel transit time and lowering volume and frequency of bowel movements (1). In contrast to other opioid receptor agonists, loperamide has poor absorption from the gastrointestinal tract and limited ability to cross the blood-brain barrier (1,2). Consequently, the drug was deemed low risk for physical dependence and abuse and since 1982 has been sold over-the-counter (OTC) (3).
Despite this labeling, there is an increasing number of reports documenting cases of loperamide misuse and abuse (3). It has only recently been discovered that loperamide is being ingested at supratherapeutic doses (>16 mg/day) for its euphoric effects or for the relief of opioid withdrawal symptoms (3,4). In 2013, online reports of recreational loperamide use at doses of 70-100mg began circulating (3). In the following three years, a 71% increase of loperamide-associated presentations to drug and poison control agencies was reported (3,6).
As a result, the cardiotoxic effects of this drug have come to light, particularly QT-prolongation and QRS- widening (3). At supratherapeutic plasma concentrations, loperamide causes a blockade of the human ether-a-go-go-related gene (hERG) cardiac potassium channel with high affinity, delaying repolarization of the cardiac myocytes and affecting QT-interval and QRS complex (5). Life-threatening dysrhythmias ensue, accounting for the increasing rate of deaths associated with loperamide overdose and toxicity (3). Reports of loperamide-associated cardiac toxicity have increased greatly in number over the past few years and include: at least 21 individual published case reports of loperamide cardiotoxicity, including one published in SWJPCC (3,7); 48 cases of serious loperamide-associated cardiac events, identified in the FDA Adverse Event Reporting System database; and 22 cases of patients found dead with elevated plasma concentrations of loperamide (3).
Loperamide is just one of an increasing number of OTC drugs with potential abuse because of the stimulant or sedative effects. Other OTC drugs commonly known for abuse are dextromethorphan, pseudoephedrine, phenylephrine, diphenhydramine and oxybutynin especially among teenagers, however, loperamide is a less commonly known drug for its opioid abuse. It is important for physicians to be aware of this increasing risk of abuse and significant life-threatening cardiotoxic effects.
References
- Killinger JM, Weintraub HS, Fuller BL. Human pharmacokinetics and comparative bioavailability of loperamide hydrochloride. J Clin Pharmacol. 1979;19:211-8. [CrossRef] [PubMed]
- Regnard C, Twycross R, Mihalyo M, et al. Loperamide. J Pain Symptom Manage. 2011;42:319-23.[CrossRef] [PubMed]
- Wu PE, Juurlink DN. Clinical review: Loperamide toxicity. Annals of Emergency Med. 2017;70:245-52. [CrossRef] [PubMed]
- Daniulaityte R, Carlson R, Falck R, et al. "I just wanted to tell you that loperamide will work": a web-based study of extra-medical use of loperamide. Drug Alcohol Depend. 2013;130:241-4. [CrossRef] [PubMed]
- Salama A, Levin Y, Jha P, et al. Ventricular fibrillation due to overdose of loperamide, the "poor man's methadone." J Community Hosp Intern Med Perspect. 2017;7(4):222-6. [CrossRef] [PubMed]
- Stanciu CN, Gnanasegaram SA. Loperamide, the "Poor Man's Methadone": Brief review. Journal of Psychoactive Drugs. 2017;49:18-21. [CrossRef] [PubMed]
- Watkins SA, Smelski G, French RNE, Insel M, Campion J. January 2019 critical care case of the month: A 32-year-old woman with cardiac arrest. Southwest J Pulm Crit Care. 2019;18(1):1-7. [CrossRef]
Cite as: Leong J, Afu K, Starobinska E, Insel M. Loperamide abuse: a case report and brief review. Southwest J Pulm Crit Care. 2020;20(2):73-5. doi: https://doi.org/10.13175/swjpcc007-20 PDF
January 2020 Critical Care Case of the Month: A Code Post Lung Needle Biopsy
Sarika Savajiyani MD and Clement U. Singarajah MBBS
Phoenix VA Medical Center
Phoenix, AZ USA
A 67-year-old man with a history of stage IIA rectal adenocarcinoma post neoadjuvant chemoradiation presented with a near code event after elective CT guided biopsy of an enlarging left lower lobe lung nodule. The patient became bradycardic and profoundly hypotensive immediately after the CT guided biopsy with the following vital signs: Systolic BP < 90 mmHg, HR 40/min sinus bradycardia, SpO2 on 100% oxygen non rebreather was 90%. Telemetry and EKG showed ST elevation in the anterior leads. He complained of vague arm and leg weakness and tingling, but did not lose consciousness or suffer a cardiac arrest.
A CT scan was performed about 2-3 minutes after the patient deteriorated (Figure 1).
Figure 1. A-E: Representative images from CT scan in soft tissue windows. Lower: Video of CT scan in soft tissue windows.
What radiographic finding likely explains the patient’s clinical deterioration? (Click on the correct answer to be directed to the second of six pages)
Cite as: Savajiyani S, Singarajah CU. January 2020 critical care case of the month: a code post lung needle biopsy. Southwest J Pulm Crit Care. 2020;20(1):1-6. doi: https://doi.org/10.13175/swjpcc042-19 PDF
October 2019 Critical Care Case of the Month: Running Naked in the Park
Spencer Jasper MD
Matthew Adams DO
Jonathan Boyd MD
Jeremiah Garrison MD
Janet Campion MD
The University of Arizona College of Medicine
Tucson, AZ USA
History of Present Illness
A 34-year-old man with a history of IV drug abuse was brought into emergency department by EMS and Tucson Police Department after complaints of naked man running and behaving erratically in a park. On arrival to emergency department patient was acting aggressively towards staff, spitting and attempting to bite. The ER staff attempted multiple times to sedate the patient with benzodiazepines, however, due to continued aggressive behavior, ongoing encephalopathy and the need for increased sedation, the patient was intubated for airway protection.
The patient was febrile (40.6° C), tachycardic (122) and hypertensive (143/86). On physical exam patient was not cooperative, was diaphoretic, cachectic, with reactive constrictive pupils, track marks in antecubital fossa bilaterally. No clonus or hypertonicity. During intubation, there was noted to be nuchal rigidity.
He was then admitted to the medical ICU. Drug intoxication from possible methamphetamines was the presumptive diagnosis of encephalopathy but given nuchal rigidity and fevers there was concern for other etiologies.
Physical Exam
- Vitals: T 40.6 °C, HR: 122, RR: 22, BP: 143/86, SpO2: 97% WT: 55 kg
- General: Intubated and sedated, cachectic
- Eye: Pupils constricted but reactive to light
- HEENT: Normocephalic, atraumatic
- Neck: Stiff, non-tender, no carotid bruits, no JVD, no lymphadenopathy
- Lungs: Clear to auscultation, non-labored respiration
- Heart: Normal rate, regular rhythm, no murmur, gallop or peripheral edema
- Abdomen: Soft, non-tender, non-distended, normal bowel sounds, no masses
- Skin: Skin is warm, dry and pink, multiple abrasions on the lower extremities bilaterally, track marks noted in the antecubital fossa bilaterally. Large abrasion with bruising around the right knee and erythema and welts on the right shin. Erythematous area on the dorsal surface of the right hand
- Neurologic: Nonfocal prior to intubation, no clonus or hypertonicity noted
Drug overdose/intoxication was presumptive diagnosis for his acute encephalopathy. Based on physical exam and vitals, what other etiologies should be considered? (click on the correct answer to be directed to the second of seven pages)
Cite as: Jasper S, Adams M, Boyd J, Garrison J, Campion J. October 2019 critical care case of the month: running naked in the park. Southwest J Pulm Crit Care. 2019;19(4):110-8. doi: https://doi.org/10.13175/swjpcc054-19 PDF
Severe Accidental Hypothermia in Phoenix? Active Rewarming Using Thoracic Lavage
Michael Mozer BS1
Guy Raz, MD2
Ryan Wyatt, MD2
Alexander Toledo, DO, PharmD2
1University of New England College of Osteopathic Medicine
Biddeford, ME USA
2Department of Emergency Medicine
Maricopa Medical Center, Phoenix, AZ USA
Abstract
Hypothermia can progress quickly and become life threatening if left untreated. Rewarming in the severely hypothermic patient is of critical importance and is achieved with active and passive techniques. Here we present a case of a hypothermic patient with cardiac instability for whom thoracic lavage was ultimately used. We will review the treatment of hypothermia and discuss the technical aspects our approach.
Case Presentation
A 53 year-old male with a past medical history of substance abuse, chronic hepatitis C, and poorly controlled type 2 diabetes mellitus complicated by a recent hospitalization for osteomyelitis was brought to the emergency department after being found lying on a road in a shallow pool of water in the early morning hours of a rainy day in Phoenix, Arizona. The ambient temperature that night was 39 °F (3.9 °C). Emergency Medical Services (EMS) noted a decreased level of consciousness and obtained a finger stick glucose of 15 mg/dl. EMS reported a tympanic membrane temperature of 23.9 °C. En route, the patient was administered 2mg naloxone and 25g dextrose intravenously with no improvement in his mental status. On Emergency Department (ED) arrival, the patient had a GCS of 8 (Eyes 4, Verbal 1, Motor 3) and exhibited intermittent posturing. His foot wound appeared clean and without signs of infection. The initial core temperature recorded was 25.9°C via bladder thermometer, systolic blood pressure was 92/50, and heart rate fluctuated between 50 and 90 beats per minute.
After removing wet clothing, initiation of warmed saline, and placing a forced warm air blanket on the patient, he was intubated for airway protection and vasopressors were initiated. Osborn waves were evident on the initial EKG (Figure 1).
Figure 1. Initial EKG with Osborn Waves (arrows).
A warmed ventilator circuit was initiated with only 0.5 °C increase in temperature in first 30 minutes. Despite these measures, he remained hypotensive and unstable. Significant laboratory findings were a white blood cell count of 25.5 thousand (92% neutrophils), lactic acid of 7.6, potassium of 5.8, serum creatinine of 1.05, glucose of 283, INR of 1.1, and urine drug screen positive for cocaine. Given his recalcitrance to norepinephrine and risk of death secondary to fatal dysrhythmia with temperatures below 28 °C intrathoracic lavage initiated.
The right hemithorax was selected for irrigation because left-sided tube placement can induce ventricular fibrillation in a perfusing patient (1). Using standard sterile technique, two 36 French thoracostomy tubes were placed; the first in the second intercostal space along the mid-clavicular line, and the second in the 5th intercostal space in the posterior axillary line (1-3). The tips of the thoracostomy tubes were oriented such that the anterior-superior tube was positioned near the right apex and the lateral-inferior tip was positioned low in the thoracic cavity (1,3). To maintain the temperature of the instilled fluid, a fluid warmer system (Level 1; Smiths Medical; Minneapolis, MN) was used and set to 41 °C. A Christmas tree adapter was used to connect the IV tubing to the superior thoracostomy tube, and a water seal chamber was attached to the inferior tube for passive drainage (3). Flow through the system was targeted to maintain steady passive drainage as described in the literature (1-6).
Thoracic cavity lavage with 41 °C saline was performed and the patient was transferred to the medical ICU after 3 hours in the ED. When he was transferred his core temperature was 29 °C and he remained on norepinephrine for hemodynamic instability. After 2 hours of continued rewarming in the MICU, his core temperature was 32 °C. Osborn waves evident on initial EKG were resolved (Figure 2).
Figure 2. Repeat EKG showing resolution of Osborn waves.
The patient left against medical advice from the hospital 4 days later neurologically intact and without sequela.
Discussion
Hypothermia can be clinically classified as mild, moderate or severe (7). Mild hypothermia, defined as core temperatures of 32-35 °C, presents with shivering. Amnesia, dysarthria, ataxia, tachycardia, and tachypnea can also be seen (1). Moderate hypothermia, defined as core temperatures of 28-32 °C, usually can present with or without shivering. Stupor, hypoventilation, paradoxical undressing and non-fatal arrhythmias such as atrial fibrillation and junctional bradycardia may also be seen (1). Patients with severe hypothermia, generally defined as temperatures below 28 °C, can present with coma, areflexia, pulmonary edema, bradycardia, and hypotension (1). There is a significant risk of fatal cardiac dysrhythmias without rapid therapeutic rewarming (1,7,8).
Rewarming in the hypothermic patient is of critical importance and is achieved with passive and/or active techniques. Attempts to limit heat loss are often unsuccessful, especially in the absence of a normal shiver response. It however remains as the first line treatment for hypothermia (8-10). Passive rewarming is attempted by the removal of cold/wet clothing and keeping the patient covered (8-10). Active external rewarming (AER) is the next line of treatment and consist of the use of externally rewarming devices such as warmed blankets, warm environment, forced air warming (Bair Hugger; 3M; Maplewood, MN) or warm hot water bladders placed in the groin and axilla (1,7-10). Active Internal Rewarming (AIR) techniques can be used to achieve more rapid increases in core temperature and are primarily utilized in cases of cardiac instability or if AER is unsuccessful (8). When available, the method of choice for active internal rewarming (AIR) is cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) as they can achieve the fastest increase in core temperature (9 °C/hr and 6 °C/hr respectively) and provide cardiovascular support (1,8,11,12). Several techniques are described in the literature that can be considered if CPB or ECMO are unavailable. These include esophageal warming devices, endovascular catheters, hemodialysis, and endocavitary lavage (1,2,4-6,13-15). While no randomized controlled trials exist, several case reports and reviews have tried to compare various techniques. These sources to do not seem to favor any particular technique over another but rather reports the rates of temperature rise (1-3,5-7,13-15). Classically, lavage techniques are attempted in the thoracic cavity, the peritoneum, the bladder, the stomach, the esophagus, or the colon. These techniques are generally coupled with warm IV fluids and warming air through the ventilator to limit loss of body heat to iatrogenic procedures during the rewarming attempt (1,7). Thoracic lavage is effective with a reported rewarming rates of 3-6 °C/hr and with excellent outcomes in case reports (1,2,4-6). Here we present a case of a hypothermic patient with cardiac instability where thoracic lavage is used and discuss the technical aspects of this approach.
Our case demonstrates the efficacy of utilizing thoracic cavity lavage for rapid rewarming in patients with severe hypothermia with a pulse and at high risk of fatal cardiac arrhythmia. In multiple case reports, thoracic lavage has been used successfully in hypothermic patients who suffered complete cardiopulmonary collapse requiring CPR (2,4,5). Although warm thoracic lavage is not the treatment of choice in these circumstances, in a facility not equipped with ECMO or CPB and a patient too unstable to transfer, it seemed to us to be the best technique. Gastric, colonic, and bladder lavage offer very minimal heat transfer due to limitations in surface area (2).
Hemodialysis would have required for us to call in a technician and would have required approval by a nephrologist at our institution. Available central venous rewarming catheters require bypass of a failsafe mechanism that does not allow rewarming to be initiated below 30 °C (1). Peritoneal lavage was a plausible choice but does not directly warm the mediastinum (2). While an open mediastinal technique has been used, we did not feel it was appropriate in a patient with a concurrent pulse (1,3). Thoracic lavage is therefore an effective alternative that should be used in cases where CPB and ECMO are unavailable especially in a patient that is hemodynamically unstable and may not survive transfer. The equipment is readily available to any Emergency Medicine or Critical Care physician. In addition, this case exemplifies the positive outcomes that are associated with rapid rewarming in the hypothermic patient with a pulse. We believe our case demonstrates the efficacy of this technique for myocardial protection from hemodynamic collapse, a topic which has not been adequately studied in the literature.
References
- Brown DJ, Danzl DF. Accidental hypothermia. In: Auerbach PS, ed. Wilderness Medicine. 7th ed. St. Louis: Mosby Inc.; 2017:135-62.
- Plaisier BR. Thoracic lavage in accidental hypothermia with cardiac arrest--report of a case and review of the literature. Resuscitation. 2005 ;66(1):99-104. [CrossRef] [PubMed]
- Schiebout JD. Hypothermic Patient Management. In: Reichman EF. eds. Reichman's Emergency Medicine Procedures, 3e New York, NY: McGraw-Hill. Available at: http://accessemergencymedicine.mhmedical.com/content.aspx?bookid=2498§ionid=201303754 (accessed August 02, 2019).
- Little G. Accidental hypothermic cardiac arrest and rapid mediastinal warming with pleural lavage: A survivor after 3.5 hours of manual CPR. BMJ Case Reports. July 2017:bcr-2017-220900. [CrossRef] [PubMed]
- Turtiainen J, Halonen J, Syväoja S, Hakala T. Rewarming a patient with accidental hypothermia and cardiac arrest using thoracic lavage. Ann Thorac Surg. 2014 Jun;97(6):2165-6. [CrossRef] [PubMed]
- Ellis MM, Welch RD. Severe hypothermia and cardiac arrest successfully treated without external mechanical circulatory support. Am J Emerg Med. 2016;34(9):1913.e5-6. [CrossRef] [PubMed]
- Tintinalli J, Stapczynski J, Ma O, Yealy D, Meckler G, Cline D. Tintinalli's Emergency Medicine. 8th ed. New York, NY: McGraw-Hill Education; 2016:1743-4.
- Brugger H, Boyd J, Paal P. Accidental Hypothermia. N Engl J Med. 2012;367(20):1930-8. [CrossRef] [PubMed]
- Paal P, Gordon L, Strapazzon G, et al. Accidental hypothermia-an update: The content of this review is endorsed by the International Commission for Mountain Emergency Medicine (ICAR MEDCOM). Scand J Trauma Resusc Emerg Med. 2016;24(1):111. [CrossRef] [PubMed]
- Zafren K, Giesbrecht GG, Danzl DF, et al. Wilderness Medical Society practice guidelines for the out-of-hospital evaluation and treatment of accidental hypothermia: 2014 update. Wilderness Environ Med. 2014 Dec;25(4 Suppl):S66-85. [CrossRef] [PubMed]
- Schober A, Sterz F, Handler C, et al. Cardiac arrest due to accidental hypothermia-A 20 year review of a rare condition in an urban area. Resuscitation. 2014;85(6):749-56. [CrossRef] [PubMed]
- Saczkowski RS, Brown DJA, Abu-Laban RB, Fradet G, Schulze CJ, Kuzak ND. Prediction and risk stratification of survival in accidental hypothermia requiring extracorporeal life support: An individual patient data meta-analysis. Resuscitation. 2018;127:51-7.[CrossRef] [PubMed]
- Primozic KK, Svensek F, Markota A, Sinkovic A. Rewarming after severe accidental hypothermia using the esophageal heat transfer device: a case report. Ther Hypothermia Temp Manag. 2018 Mar;8(1):62-4. [CrossRef] [PubMed]
- Murakami T, Yoshida T, Kurokochi A, et al. Accidental hypothermia treated by hemodialysis in the acute phase: three case reports and a review of the literature. Intern Med. 2019 Jun 7. [CrossRef]
- Klein LR, Huelster J, Adil U, et al. Endovascular rewarming in the emergency department for moderate to severe accidental hypothermia. Am J Emerg Med. 2017 Nov;35(11):1624-9. [CrossRef] [PubMed]
Cite as: Mozer M, Raz G, Wyatt R, Toledo A. Severe accidental hypothermia in Phoenix? Active rewarming using thoracic lavage. Southwest J Pulm Crit Care. 2019;19(2):79-83. doi: https://doi.org/10.13175/swjpcc038-19 PDF
Left Ventricular Assist Devices: A Brief Overview
Bhargavi Gali MD
Department of Anesthesiology and Perioperative Medicine
Division of Critical Care Medicine
Mayo Clinic Minnesota
Rochester, MN, USA
Introduction
Second and third generation left ventricular assist devices (LVAD) have been increasingly utilized as both a bridge to transplantation and as destination therapy (in patients who are not considered transplant candidates) for advanced heart failure. Currently approximately 2500 LVADs are implanted yearly, with an estimated one year survival of >80% (1). Almost half of these patients undergo implantation as destination therapy. A recent systematic review and meta-analysis found no difference in one-year mortality between patients undergoing heart transplantation in comparison with patients undergoing LVAD placement (2).
Early LVADs were pulsatile pumps, but had multiple limitations including duration of device function, and requirement for a large external lead that increased risk of infection. Currently utilized second and third generation devices are continuous flow (first generation were pulsatile flow). Second generation devices have axial pumps (HeartMate II®). The third generation LVADs ((HeartMate III®), HVAD®) are also continuous flow, with centrifugal pumps, which are thought to decrease possibility of thrombus formation and increase pump duration in comparison to the second generation axial pumps. It is also felt that a lack of mechanical bearings contributes to this effect.
LVADs support circulation by either replacing or supplementing cardiac output. Blood is drained from the left ventricle with inflow cannula in the left ventricular apex to the pump, and blood is returned to the ascending aorta via the outflow cannula (3) (Figure 1).
Figure 1. Third generation Left Ventricular Assist Device. Heartware System ™. Continuous flow left ventricular assist device (LVAD) configuration. One of the third generation LVADs is the HeartWare System. With this device the inflow cannula is integrated into the pump. The pump is attached to the heart in the pericardial space, with the outflow cannula in the aorta. A driveline connects the device to the control unit. This control unit is attached to the two batteries. (Figure used with permission from Medtronic).
The device assists the left ventricle by the action of the axial (second generation) or centrifugal (third generation) pump that rotates at a very high speed and ejects the blood into the aorta via the outflow cannula. A tunneled driveline connects the pump to the external controller that operates the pump function. The controller connects to the power source via two cables, which can be battery or module-powered.
LVADs offload volume from the left ventricle, and decrease left ventricular work. Pulmonary pressures and the trans pulmonary gradients are also decreased by the reduced volume in the left ventricle (4). End organ perfusion is improved secondary to enhanced arterial blood pressure and micro perfusion.
There are four main parameters of pump function:
- Pump speed: the speed at which the LVAD rotors spin, and is programmed. Measured in RPM.
- Pump power: the wattage needed to maintain speed and flow, which is the energy needed to run the pump. Measured in Watts.
- Pump flow: estimate of the cardiac output, which is the blood returned to the ascending aorta, and is based on pump speed and power. Measure in L/min
- Pulsatility index (PI): a calculated value that indicates assistance the pump provides, in relation to intrinsic left ventricular A higher number indicates higher left ventricular contribution to pulsatile flow.
The cardiac output of currently utilized LVADs is directly related to pump speed and inversely related to the pressure gradient across the pump. As the pump speed is fixed, right ventricular failure can decrease the volume of blood transmitted to the pump and decrease LVAD flow (3, 4). With right ventricular failure, inotropic support may be needed to improve the LVAD pump flow. High afterload, such as may be seen with an increase in systemic vascular resistance can decrease pump flow.
Complications
Adverse events occur in more than 70% of LVAD patients in the first year (5). These complications include infections, bleeding, stroke, and LVAD thrombosis. More than 50% of patients are readmitted within the first 6 months after LVAD implantation (6).
Driveline infections are the most commonly reported LVAD infection, and are the most likely to respond to treatment (7). Pump pocket infections may require debridement plus/minus antibiotic bead placement. Bloodstream infections are less commonly reported, and more difficult to treat, and many patients are placed on chronic suppressive antibiotic therapy (7). There is a possible association between stroke and bloodstream infection, reported in some studies. Patients who were younger and had a higher body mass index were noted to have a higher incidence of LVAD infections.
Gastrointestinal bleeding is a major cause of nonsurgical bleeding, reported in almost 30% of patients after LVAD placement (1). Patients may develop acquired von Willebrand factor deficiency secondary to high shear forces in the LVAD that lead to breakdown of von Willebrand protein (6). Antithrombotic therapy is commonly instituted after LVAD implantation which also increases risk of bleeding. A high incidence of arteriovenous malformations is reported in these patients, although the etiology is not clear. Transfusion, holding antithrombotic therapy, and identifying possible sources are included in the standard approach to management.
There is a high risk of both ischemic and hemorrhagic strokes in the first year after LVAD placement (8). Surgical closure of the aortic valve and off-axis positioning of the cannulas have been suggested as altering shear forces, increasing thrombotic risk, and thus risk of stroke. Post-surgical risks may include pump thrombosis, infections, supratherapeutic INR, and poorly controlled hypertension. Early diagnosis has led to consideration of interventions such as thrombectomy (8).
LVAD thrombosis can occur on either cannula (inflow or outflow) or the pump. Typically patients receive ongoing anticoagulation, commonly with warfarin, and antiplatelet agents, and often aspirin. Heartmate II® may have higher rate of thrombosis than HVAD or Heart Mate 3, although this is under debate (6). Thrombotic complications range in severity from asymptomatic increase in lactate dehydrogenase or plasma-free hemoglobin, to triggering of LVAD alarms, up to development of heart failure. The inflow and outflow cannulas and pump can be the site of thrombosis. Management typically involves revising the antithrombotic management. If there is no improvement or worsening, replacement of LVAD may be indicated. There is limited evidence to suggest that systemic thrombolysis may be of benefit in treating pump thrombosis, particularly in regards to the HVAD, though better data would be useful
Procedural Management
When a patient with an LVAD requires non cardiac surgery, optimal management includes having an on-site VAD technician, and close involvement of VAD cardiology and cardiac surgery in consultation. Anticoagulation will often be transitioned to heparin infusion prior to elective procedures (9). Suction events (LV wall is sucked into the inflow cannula) can occur secondary to under filled left heart, and this can become more apparent perioperatively. This can also decrease right heart contractility by moving the interventricular septum to the left, and thus decrease cardiac output. Management often involves fluid bolus. Suction events can lead to decreased flow, left ventricular damage, and ventricular arrhythmias. Hemodynamic management can be challenging with non-pulsatile flow, and placement of an arterial line can facilitate optimal management. Postoperative care in a monitored setting is beneficial in case of further volume related events and to watch for bleeding.
Emergent Complications
Arrhythmias occur in many patients after LVAD implantation. Atrial arrhythmias are reported in up to half of LVAD patients, and ventricular arrhythmias in 22-59% (10, 11). Loss of AV synchrony can lead to decreased LV filling and subsequent RV failure. Rhythm or rate control with rapid atrial arrhythmias is necessary to decrease development of heart failure. Ventricular arrhythmias may be hemodynamically tolerated for some time secondary to the LVAD support (6). If there is concern that the inflow cannula is touching the LV septum, as may occur with severe hypovolemia, echocardiography can help determine if volume resuscitation should be the initial step in treating ventricular arrhythmia.
If cardiac arrest occurs, the first step of cardiopulmonary resuscitation in patients with LVAD is assessment of appropriate perfusion via physical examination (12). If perfusion is poor or absent, assessment of LVAD function should take place. If the LVAD is not functioning appropriately, checking for connections and power is the next step. If unable to confirm function or restart LVAD, chest compressions are indicated by most recent guidelines from the American Heart Association. There is always concern of dislodgement of LVAD cannula or bleeding during these situations.
Conclusion
Currently implanted LVADS are continuous flow, and provide support via a parallel path from the left ventricle to the aorta. As the number of patients with LVADs increase all medical providers should have a basic understanding of the function and common complications associated with these devices. This will enhance the ability to initiate appropriate care.
References
- Kirklin JK, Pagani FD, Kormos RL, et al. Eighth annual INTERMACS report: Special focus on framing the impact of adverse events. J Heart Lung Transplant. 2017 Oct;36(10):1080-6. [CrossRef] [PubMed]
- Theochari CA, Michalopoulos G, Oikonomou EK, et al. Heart transplantation versus left ventricular assist devices as destination therapy or bridge to transplantation for 1-year mortality: a systematic review and meta-analysis. Annals of Cardiothoracic Surgery. 2017;7(1):3-11. [CrossRef] [PubMed]
- Lim HS, Howell N, Ranasinghe A. The physiology of continuous-flow left ventricular assist devices. J Card Fail. 2017;23(2):169-80. [CrossRef] [PubMed]
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- Miller LW, Rogers JG. Evolution of left ventricular assist device therapy for advanced heart failure: a review. JAMA Cardiol. 2018 Jul 1;3(7):650-8. [CrossRef] [PubMed]
- DeVore AD, Patel PA, Patel CB. Medical management of patients with a left ventricular assist device for the non-left ventricular assist device specialist. JACC Heart Fail. 2017 Sep;5(9):621-31. [CrossRef] [PubMed]
- O'Horo JC, Abu Saleh OM, Stulak JM, Wilhelm MP, Baddour LM, Rizwan Sohail M. Left ventricular assist device infections: a systematic review. ASAIO J. 2018 May/Jun;64(3):287-294. [CrossRef] [PubMed]
- Goodwin K, Kluis A, Alexy T, John R, Voeller R. Neurological complications associated with left ventricular assist device therapy. pert Rev Cardiovasc Ther. 2018 Dec;16(12):909-17. [CrossRef] [PubMed]
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Cite as: Gali B. Left ventricular assist devices: a brief overview. Southwest J Pulm Crit Care. 2019;19(2):68-72. doi: https://doi.org/10.13175/swjpcc039-19 PDF
July 2019 Critical Care Case of The Month: An 18-Year-Old with Presumed Sepsis and Progressive Multisystem Organ Failure
Robert A. Raschke, MD
The University of Arizona College of Medicine – Phoenix
Phoenix, AZ USA
History of Present Illness
An 18-year-old female student from Flagstaff was transferred to our hospital for refractory sepsis. She had presented with a 2 week history of fever, malaise, sore throat, myalgias, arthralgias and a rash.
PMH, SH and FH
She reported no significant past medical history or family history. She attended cosmetology school, denied smoking or drug abuse and was sexually monogamous. She had only traveled in-state, did not hike or camp and her only animal exposure was playing with her two pet Great Danes.
Physical Examination
The patient had a fever of 38.5°C. on original presentation. HEENT exam was reported as unrevealing. Lungs were clear. There were no heart murmurs and the abdominal exam was unremarkable. No joint effusions were apparent. A rash was mentioned, but not described and it apparently disappeared shortly after admission.
Initial laboratory testing was significant for WBCC of 12.1 K/mm3, creatinine of 1.5 mg/dL and AST of 45 IU/L. A rapid influenza screen, urinalysis and chest radiography were unrevealing. Blood cultures were drawn and intravenous fluids, piperacillin/tazobactam and azithromycin were administered. Over the next four days, the fever persisted and the blood cultures resulted in no growth. Serial laboratory values demonstrated progressive worsening in renal function and increasing hepatic enzymes. The patient became dyspneic and developed rales and progressive hypoxia prompting transfer.
On arrival in our ICU, the patient was alert, in mild respiratory distress and hypotensive to 78/43 mmHg, requiring immediate initiation of intravenous norepinephrine. She reported nausea and severe diffuse myalgia and arthralgia. On examination, she was ill-appearing with blood pressure 101/58 (on norepinephrine at 25 mcg/min), heart rate 104 beats/min, respiratory rate 33 breaths/min, temperature 38.8°C. She had mild oropharyngeal erythema, some shotty cervical lymph nodes, bilateral rales, mild epigastric and right upper quadrant tenderness, and a macular erythematous rash approximately 14 x 29 cm on her left forearm that disappeared within several hours.
Her ICU admission chest x-ray is shown in Figure 1.
Figure 1. Admission ICU portable chest X-ray showing bilateral areas of consolidation.
Her laboratory evaluation showed the following:
- WBCC: 2,500/mm3 63% segs with toxic granulation/vacuolated segs
- Hemoglobin/Hematocrit: 7.9 g/dL/26.7%
- Platelets: 50,000/mm3
- BUN/creatinine: 23/1.25 mg/dL
- AST/ALT: 246/189 IU/L (normal 10-40 and 7-56)
- PT: 20.9 sec
- Lactate: 4.5 mmol/L
- Urinalysis: bland sediment, without bacteria or leukocytes
- ABG: 7.33, pCO2 34, pO2 78 (on 45% FiO2 by ventimask)
- Transthoracic echocardiogram showed normal LV and RV size and systolic function with no vegetations
- US abdomen showed hepatosplenomegaly, retroperitoneal lymphadenopathy, and normal kidneys and ureters.
What are diagnostic considerations at this time? (Click on the correct answer to be directed to the second of six pages)
- Rocky mountain spotted fever (RMSF)
- Acute retroviral syndrome
- Still’s disease
- Systemic lupus erythematosus (SLE)
- All of the above
Cite as: Raschke RA. July 2019 critical care case of the month: an 18-year-old with presumed sepsis and progressive multisystem organ failure. Southwest J Pulm Crit Care. 2019;19(1):1-9. doi: https://doi.org/10.13175/swjpcc043-19 PDF
Amniotic Fluid Embolism: A Case Study and Literature Review
Ryan J Elsey DO1*, Mary K Moats-Biechler OMS-IV2, Michael W Faust MD3, Jennifer A Cooley CRNA-APRN4, Sheela Ahari MD4, and Douglas T Summerfield MD1
Departments of Internal Medicine1,Obstetrics and Gynecology3,and Anesthesia4
1Mercy Medical Center—North Iowa
Mason City, IA USA
2A.T. Still University
Kirksville, MO USA
Abstract
Amniotic fluid embolus is a rare and life threatening peripartum complication that requires quick recognition and emergent interdisciplinary management to provide the best chance of a positive outcome for the mother and infant. The following case study demonstrates the importance of quick recognition as well as an interdisciplinary approach in caring for such a condition. A literature review regarding the current recommendations for management of this condition follows as well as a proposed treatment algorithm.
Introduction
Amniotic fluid embolus (AFE) is a rare and life-threatening complication of pregnancy; a recent population-based review found an estimated incidence ranging from 1 in 15,200 deliveries in North America and 1 in 53,800 deliveries in Europe (1). Mortality rates vary but have been reported to range from 11% to more than 60%, with the most recent population-based studies in the United States reporting a 21.6% fatality rate (1-4). Despite best efforts, it remains one of the leading causes of maternal death (1,5,6). However, rapid diagnosis of AFE and immediate obstetric and intensive care has proven to play a decisive role in maternal prognosis and survival (7-9).
In 2016, uniform diagnostic criteria were proposed for reporting on cases of AFE. First, a report of AFE requires a sudden onset of cardiorespiratory arrest, which consists of both hypotension (systolic blood pressure < 90 mmHg) and respiratory compromise (dyspnea, cyanosis, or SpO2 < 90%). Secondly, overt disseminated intravascular coagulation (DIC) must be documented following the appearance of signs or symptoms using a standardized scoring system. Coagulopathy must be detected prior to a loss of sufficient blood to account for dilutional or shock-related consumptive coagulopathy. Third, the clinical onset must occur during labor or within 30 minutes of delivery of the placenta. Fourth, no fever ≥ 38.0° C during labor can occur (10).
The following case study qualifies as a reportable incidence of an AFE under the above criteria and further demonstrates the ability to successfully stabilize a patient with AFE due to quick recognition, interdisciplinary cooperation, and effective supportive management.
Case Presentation
A 34-year-old gravida 5, para 1-1-2-2, presented at 36 weeks and 1-day gestation for induction of labor. Her past medical history included esophageal atresia at birth and a past pregnancy complicated by preterm, premature rupture of the membranes. Initial labs at admission were significant for a hemoglobin of 12.2 g/dL and a platelet count of 234 x103 u/L. The patient was subsequently started on lactated ringers at 125 ml/hr. As the patient's labor progressed, an epidural was placed 3 hours after admission. Four hours and 42 minutes after admission, an artificial rupture of the membranes was performed.
Eighteen minutes after the artificial rupture of the membranes was performed, the patient was noted to have seizure-like activity. She was given an intravenous (IV) fluid bolus and ephedrine, and the anesthesia provider was emergently contacted. When anesthesia arrived, the patient was noted to be cyanotic in bed. Patient vitals and exam were significant for emesis, a heart rate of 50 beats per minute (bpm), systolic blood pressure in the low 70s (mmHg), and a fetal heart rate in the 70s.
The differential diagnosis at this time was broad and included anesthesia drug reactions such as an intravascular epidural migration, pulmonary thromboembolism, eclampsia, or even an aortic dissection. A pulmonary embolism was felt to be unlikely due to the patient's bradycardia and sudden neurologic changes. Eclampsia was less likely at the time due to no signs of pre-eclampsia in the patient as well as the patient's current bradycardia and hypotension. Given the patient's absence of Marfan syndrome, aortic dissection was not considered to be a high probability. The patient did have signs consistent with an intravascular epidural including altered mental status, cyanosis, bradycardia, hypotension, vomiting, and a low fetal heart rate. However, at the time anesthesia felt she was more likely suffering from an acute embolic process given the timeframe between the artificial rupture of the membranes and the onset of her symptoms.
Given the patient's instability, she was emergently taken for a cesarean section and intubated to provide airway stabilization. The cesarean section began 15 minutes after seizure like symptoms started and upon delivery, the infant was subsequently transferred to a tertiary center for therapeutic hypothermia.
Intraoperatively, the patient was noted to maintain a peripheral capillary oxygen saturation (SpO2) of >90%. However, end tidal C02 was elevated to 54 mmHg despite hyperventilation and peak airway pressures were elevated to 38 cmH2O. Albuterol and sevoflurane were subsequently utilized in an attempt to increase bronchodilation. Following completion of the caesarian section, peak airway pressures normalized to less than 30 cmH2O but end tidal CO2 levels remained as high as 52 mmHg despite hyperventilation. Blood pressure was significant for systolic pressure of 80 mmHg. IV phenylephrine was administered. Additionally, uterine massage was performed to aid in hemorrhage control and the patient was administered IV oxytocin, methylergonovine maleate, carboprost, and vaginal misoprostol. A repeat complete blood count was performed one hour after symptom onset which showed a hemoglobin of 10.3 g/dL and a platelet count of 103 x103 u/L.
In this case, the patient’s care team had a high suspicion of an AFE with symptoms that followed the uniform diagnostic criteria for an AFE. The patient had hemodynamic instability, coinciding with the recent rupture of membranes. Her systolic blood pressure was < 90 mmHg and her end tidal C02 levels (in mmHg) were elevated to the high 40s and low 50s. The critical care team was notified of her condition and the patient was subsequently transferred to the Intensive Care Unit (ICU) on mechanical ventilation and sedated with fentanyl and versed.
Upon arrival to the ICU, a DIC panel was performed revealing DIC. Labs showed a fibrinogen level of 52 mg/dL, A D-dimer greater than 128,000 ng/mL, and a platelet count of 80,000 u/L despite the administration of one pooled unit of platelets. The patient's international normalized ratio (INR) was 1.3 with a baseline INR of 0.9. Due to multiple laboratory abnormalities and a clinical condition consistent with DIC, aggressive transfusions were performed per the standard of care for patients suffering with DIC. A peripheral smear was obtained revealing schistocytes (Figure 1) which verified the DIC diagnosis.
Figure 1. The patient's peripheral blood smear four hours after onset of symptoms which demonstrates schistocytes indicative of DIC.
Hematology was emergently consulted and it was recommended to avoid additional platelet transfusions unless platelet counts dropped below 10,000 to 20,000 u/L. One milligram (mg) of subcutaneous phytonadione was also given five hours after symptom onset in an effort to decrease bleeding.
Cardiology was consulted and performed an emergent echocardiogram to assess the patient’s heart function and rule out any cardiac abnormalities. Given her past history of esophageal atresia, there was particular concern about an underlying ventricular septal defect, patent ductus arteriosus, or tetralogy of Fallot (11). The echocardiogram revealed a dilated, yet functional right ventricle, which was expected in the setting of an AFE. ICU physicians at a tertiary care center were provisionally consulted to confirm that the patient was a candidate for arteriovenous extracorporeal membrane oxygenation (AV-ECMO) should she suffer further cardiopulmonary collapse. Labs, including hemoglobin, platelets, fibrinogen activity, and ionized calcium were drawn every two hours during the acute phase of the patient's management and abnormalities were addressed as required over the subsequent two hours. The patient's hemoglobin was noted to decline to as low as 6.7 g/dL. Of note, lab draws did suffer some sample lysis due to the patient's coagulation abnormalities. The patient did initially require phenylephrine for blood pressure support. Additionally, she was placed on an experimental septic shock protocol which involved the administration of 1500 mg of ascorbic acid every six hours, 60 mg of methylprednisolone every six hours, and 200 mg of thiamine every 12 hours. The patient began to stabilize around 10 to 12 hours after her AFE symptoms began and pressor support was titrated off, at which point blood draws were liberalized to every four hours. The patient continued to improve and remained stable overnight.
On hospital day two, the patient was noted to be alert and was successfully extubated. Following extubation, the physical exam found her to be neurologically and hemodynamically intact. During her stay in the ICU, the patient received a total of eight units of packed red blood cells, five units of fresh frozen plasma, one pooled unit of platelets, and one unit of cryoprecipitate. The patient was ultimately discharged from the hospital on day four with no long-term sequelae noted.
The patient was informed that data from the case would be submitted for publication and gave her consent.
A Review of the Literature
AFE remains one of the leading causes of direct, maternal mortality among developed countries (1,12,13). Multiple reviews have studied the incidence of AFE, which varies widely, from 1.9 per 100,000 to 7.7 per 100,000 pregnancies, with the reported fatality rate due to AFE ranging from 11% to more than 60%, depending on the study (1,2,4,14). The difficulty in reporting an accurate incidence and fatality rate is likely secondary to the fact that AFE remains a diagnosis of exclusion. AFE is traditionally diagnosed clinically during labor in a woman with ruptured membranes and a triad of symptoms, including unexplained cardiovascular collapse, respiratory distress, and DIC. (1,2,15-18). Additional symptoms may include hypotension, frothing from the mouth, fetal heart rate abnormalities, loss of consciousness, bleeding, uterine atony, and seizure-like activity (15,16,19).
The majority of women who fail to survive an AFE die during the acute phase (median of one hour and 42 minutes after presentation) (2,6). Surviving beyond the acute phase dramatically improves their overall chance of survival; however, survival is not without long term morbidities. Analysis performed in the United Kingdom in 2005 and again in 2015 showed that 7% of woman surviving AFE have permanent neurological injury, including persistent vegetative state/anoxic/hypoxic brain injury or cerebrovascular accident (2,7). Among survivors,17% were shown to have other comorbidities, including sepsis, renal failure, thrombosis or pulmonary edema and 21% required a hysterectomy (2,6).
Despite several decades of research, the pathogenesis of an AFE continues to remain somewhat clouded. Multiple theories have been postulated concerning the clinical manifestations occurring with an AFE and their relationship with the passage of amniotic fluid into the systemic maternal circulation. The first theory proposed described amniotic debris passing through the veins of the endocervix and into maternal circulation, resulting in an obstruction (1,6). This theory has fallen out of favor as there is no physical evidence of obstruction noted on radiologic studies, autopsies, or experimentally in animal models (1,20,21). Additionally, multiple studies have found that that the passage of amniotic and fetal cells into maternal circulation are very common during pregnancy and delivery (6). Thus, most theories today focus on humoral and immunological factors and how they affect the body (5,22,23). Current research focuses on the effect of amniotic fluid on the body after it has already entered into maternal circulation. It is theorized that the amniotic fluid results in the release of various endogenous mediators, resulting in the physiologic changes that are seen with an AFE. Proposed mediators include histamine (22), bradykinin (24), endothelin (25,26), leukotrienes (27), and arachidonic acid metabolites (28).
The hemodynamic response to AFE is biphasic in nature. It consists of vasospasm, resulting in severe pulmonary hypertension, and intense vasoconstriction of the pulmonary vasculature secondary to the amniotic fluid itself, which can lead to ventilation-perfusion mismatch and resultant hypoxia (5,6,29). On an echocardiogram, the initial phase of an AFE consists of right ventricular failure demonstrated by a severely dilated, hypokinetic right ventricle with deviation of the interventricular septum into the left ventricle (18). Following the initial phase of right ventricular failure, which can lasts minutes to hours, left ventricular failure along with cardiogenic, pulmonary edema becomes the prominent finding (1,5). This occurs due to a reduction in preload as well as systemic hypotension. These changes may decrease coronary artery perfusion, which can result in myocardial injury, precipitation of cardiogenic shock, and worsening of distributive shock (1,6,30).
DIC is present in up to 83% of patients experiencing an AFE; however, its onset during presentation can be variable (31). It may present within the first ten minutes following cardiovascular collapse, or it may precipitate up to nine hours following the initial clinical manifestation (5,31,32). The precipitating pathophysiology behind DIC in AFE is poorly understood, but is likely to be consumptive, rather than fibrinolytic, in nature. In an AFE it is currently theorized that tissue factor, which is present in amniotic fluid, activates the extrinsic pathway by binding with factor VII, triggering clotting to occur by activating factor X, resulting in the consumptive coagulopathy (1,33-35). Ultimately, it is felt that this coagulation leads to vasoconstriction of the microvasculature and thrombosis by producing thrombin that is secreted into the endothelin, leading to the changes seen in DIC (1,5,6,14,18).
Recommended Management for AFE Based on Current Literature
Early recognition of AFE and immediate obstetric and intensive care has proven to play a decisive role in maternal prognosis and survival (7,8). In order to survive an an AFE, patients require immediate multidisciplinary management with a focus on maintaining oxygenation, circulatory support, and correcting coagulopathy (1,6).
A literature review of the current management for patients presenting with AFE recommends standard initial lifesaving supportive care. This should begin with immediate protection of the patient's airway via endotracheal intubation and early, sufficient oxygenation using an optimized positive end-expiratory pressure (FiO2:PEEP) ratio, which also decreases the risk of aspiration (1,5,29). Two large bore IV lines should be placed for crystalloid fluid resuscitation. In the setting of a cardiopulmonary arrest, cardiopulmonary resuscitation should be initiated and an immediate caesarian section within three to five minutes should be performed in the presence of a fetus ≥ 23 weeks gestation (5,18,36-38). This serves several purposes, including decreasing the risk of the infant suffering from long term neurologic injury secondary to hypoxia, improving venous flow to the right heart by emptying the uterus, and reducing pressure on the inferior vena cava to decrease impedance to blood flow, which decreases systemic blood pressure (1,5,31,39,40).
During the initial phase, attention should be paid to avoid hypoxia, acidosis, and hypercapnia due to their ability to increase pulmonary vascular resistance and lead to worsening of right heart failure and recommendations include sildenafil, inhaled or injected prostacyclin, and inhaled nitric oxide (6). Recommendations to treat for hypotension during this phase include the utilization of vasopressors, such as norepinephrine or vasopressin (1,6,18,37,41). Hemodynamic management during the second phase should focus on the patient's left-sided heart failure by optimizing cardiac preload via vasopressors to maintain perfusion and utilizing inotropes such as dobutamine or milrinone to increase left ventricular contractility (1,6,18).
Due to the relationship between AFE and DIC, current recommendations suggest early assessment of the patient's coagulation status. Additionally, in the setting of a massive hemorrhage, blood product administration should not be delayed while awaiting laboratory results (18). Early corrective management of the patient's coagulopathy should be aggressive in nature, especially in the setting of a massive hemorrhage. Tranexamic acid and fibrinogen concentrate (for fibrinogen levels below 2 g/L) are essential in the treatment of hyper-fibrinolysis. Additionally, multiple obstetric case studies have shown fibrinogen replacement to benefit from bedside rotational thromboelastometry if available due to its ability to rapidly diagnosis consumptive versus fibrinolytic coagulopathy at the bedside (5,42,43). Hemostatic resuscitation with packed red blood cells, fresh-frozen plasma, and platelets at a ratio of 1:1:1 should be administered (6,18). Cryoprecipitate replacement is recommended as well due to the consumptive nature of DIC in AFE, and its importance should not be understated. A 2015 population-based cohort study showed that women with AFE who died or had permanent neurologic injury were less likely to have received cryoprecipitate than those who survived and were without permanent neurologic injury (1,2). Furthermore, due to the dynamic processes of chemodynamical labs, including hemoglobin, platelet count, and fibrinogen must be monitored closely to prevent complications or over transfusion (14).
Uterine atony is a common feature with AFE and it is recommended to immediately administer uterotonics during the postpartum period to prevent its occurrence (5,44). Should it occur, uterine atony should be managed aggressively via uterotonics such as oxytocin, ergot derivatives, and prostaglandins; refractory cases may require packing material for uterine tamponade, uterine artery ligation, or even a hysterectomy for the most severe (5,8,18).
In addition to the treatments listed above, multiple case reports support the use of aggressive or novel therapeutic modalities to aid in the treatment of AFE; however, for many of the treatments, evidence supporting increased survival of an AFE is merely anecdotal (18). Among the best supported ancillary treatments is nonarterial extracorporeal membrane oxygenation as a possible therapeutic treatment for patients with refractory acute respiratory distress syndrome. However, due to the profoundly coagulopathic state of AFE and the active hemorrhage occurring with AFE, the use of anticoagulation may profoundly worsen bleeding. Consequently, extracorporeal membrane oxygenation is controversial and not routinely recommended in the management of AFE (6,18). Similarly, post-cardiac arrest therapeutic hypothermia with a range of 32°C to 34°C is often avoided in patients with AFE due to the increased risk of hemorrhage given their predisposition for DIC (18). However, in patients not demonstrating DIC and overt bleeding, targeted temperature management to 36°C and preventing hyperthermia is an option that should be considered (17,45,46). Factor VIIa procoagulant, which increases thrombin formation, has been utilized anecdotally, but strong supporting data is lacking; it should only be considered if following the replacement with massive coagulation factors, hemostasis and bleeding fail to improve (5,47). Additionally, it is important to note that factor VIIa replacement is only effective if other clotting factors have been replaced (1,6,48,49). Novel therapeutic modalities mentioned in the literature also include continuous hemofiltration, cardiopulmonary bypass, nitric oxide, steroids, C1 esterase inhibitor concentrate, and plasma exchange transfusion. While there are case reports published to suggest that all of the aforementioned therapies may provide some level of improvement in patients with AFE, the positive results from these cases may be due to their administration during the intermediate phase of AFE as opposed to the acute phase of AFE, where the majority of mortality occurs—once patients have surpassed the early, acute phase, survival chances greatly improve with continued supportive care (1,6).
AFE has traditionally been viewed as a condition associated with poor outcomes and a high mortality rate for both the mother and the infant. However, with quick AFE recognition, high quality supportive care, and interdisciplinary cooperation, patients can have positive outcomes. Based on the success with the patient presented in this case and the review of the current literature as seen above, the authors have proposed an algorithm (Figure 2) for the treatment of future patients experiencing AFE.
Figure 2. Proposed interdisciplinary treatment algorithm for acute management of an AFE.
By following the algorithm, the authors believe that the outcomes for AFE patients can be improved.
Abbreviations
PEEP: positive end-expiratory pressure; BP: blood pressure; TV: tidal volume; ACLS: Advanced cardiac life support; ABG: Arterial blood gas; CBC: Complete blood count; CMP: Complete metabolic profile; INR: International normalized ratio; PTT: Partial prothrombin time; ART line: Arterial line; NO: Nitric oxide; ARDS: Acute respiratory distress syndrome; ECMO: Extracorporeal membrane oxygenation; FFP: Fresh frozen plasma; Plt: Platelet; pRBCs: Packed red blood cells; NE: Norepinephrine.
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- Dean LS, Rogers RP,3rd, Harley RA, Hood DD. Case scenario: amniotic fluid embolism. Anesthesiology. 2012;116(1):186-92. [CrossRef] [PubMed]
- Lockwood CJ, Bach R, Guha A, Zhou XD, Miller WA, Nemerson Y. Amniotic fluid contains tissue factor, a potent initiator of coagulation. Am J Obstet Gynecol.1991;165(5 Pt 1):1335-41. [CrossRef] [PubMed]
- McDougall RJ, Duke GJ. Amniotic fluid embolism syndrome: case report and review. Anaesth Intensive Care. 1995;23(6):735-40. [CrossRef] [PubMed]
- Uszynski M, Zekanowska E, Uszynski W, Kuczynski J. Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in amniotic fluid and blood plasma: implications for the mechanism of amniotic fluid embolism. Eur J Obstet Gynecol Reprod Biol. 2001;95(2):163-6. [CrossRef] [PubMed]
- Jeejeebhoy FM, Zelop CM, Lipman S, et al. Cardiac Arrest in Pregnancy: A Scientific Statement from the American Heart Association. Circulation. 2015;132(18):1747-73. [CrossRef] [PubMed]
- O'Shea A, Eappen S. Amniotic fluid embolism. Int Anesthesiol Clin. 2007;45(1):17-28. [CrossRef] [PubMed]
- Davies S. Amniotic fluid embolus: a review of the literature. Can J Anaesth. 2001;48(1):88-98. [CrossRef] [PubMed]
- Martin RW. Amniotic fluid embolism. Clin Obstet Gynecol. 1996;39(1):101-6. [CrossRef] [PubMed]
- Martin PS, Leaton MB. Emergency. Amniotic fluid embolism. Am J Nurs. 2001;101(3):43-44. [CrossRef] [PubMed]
- Moore J, Baldisseri MR. Amniotic fluid embolism. Crit Care Med. 2005;33(10 Suppl):S279-285.[CrossRef] [PubMed]
- Collins NF, Bloor M, McDonnell NJ. Hyperfibrinolysis diagnosed by rotational thromboelastometry in a case of suspected amniotic fluid embolism. Int J Obstet Anesth. 2013;22(1):71-6. [CrossRef] [PubMed]
- Loughran JA, Kitchen TL, Sindhaker S, Ashraf M, Awad M, Kealaher EJ. Rotational thromboelastometry (ROTEM®)-guided diagnosis and management of amniotic fluid embolism. Int J Obstet Anesth. 2018. Sep 11. pii: S0959-289X(18)30122-5. [CrossRef] [PubMed]
- Tuffnell D, Knight M, Plaat F. Amniotic fluid embolism - an update. Anaesthesia. 2011;66(1):3-6. [CrossRef] [PubMed]
- Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 C versus 36 C after cardiac arrest. N Engl J Med. 2013;369(23):2197-206. [CrossRef] [PubMed]
- Callaway CW, Donnino MW, Fink EL, et al. Part 8: Post-cardiac arrest care: 2015 American Heart Association Guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 Suppl 2):S465-82. [CrossRef] [PubMed]
- Leighton BL, Wall MH, Lockhart EM, Phillips LE, Zatta AJ. Use of recombinant factor VIIa in patients with amniotic fluid embolism: a systematic review of case reports. Anesthesiology. 2011;115(6):1201-8. [CrossRef] [PubMed]
- Prosper SC, Goudge CS, Lupo VR. Recombinant factor VIIa after amniotic fluid embolism and disseminated intravascular coagulopathy. Obstet Gynecol. 2007;109(2 pt 2):524-5. [CrossRef] [PubMed]
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Cite as: Elsey RJ, Moats-Biechler MK, Faust MW, Cooley JA, Ahari S, Summerfield DT. Amniotic fluid embolism: A case study and literature review. Southwest J Pulm Crit Care. 2019;18(4):94-105. doi: https://doi.org/10.13175/swjpcc105-18 PDF
April 2019 Critical Care Case of the Month: A Severe Drinking Problem
Francisco J. Marquez II MD
Department of Pulmonary and Critical Care Medicine
Banner University Medical Center/University of Arizona – Phoenix
Phoenix, AZ USA
History of Present Illness
A 55-year-old Caucasian man, presented to an outside hospital with altered mental status.
Past Medical/Social History
- Severe alcohol and intermittent fentanyl abuse
- Homelessness
Physical Exam
- Hypothermic and hypertensive.
- Patient encephalopathic without any acute deficits
- Pupils are normal sized and react to light
Which of the following should be obtained or done in his initial evaluation? (Click on the correct answer to proceed to the second of six pages)
Cite as: Marquez FJ II. April 2019 critical care case of the month: A severe drinking problem. Southwest J Pulm Crit Care. 2019;18(4):67-73. doi: https://doi.org/10.13175/swjpcc003-19 PDF
January 2019 Critical Care Case of the Month: A 32-Year-Old Woman with Cardiac Arrest
Sarah A. Watkins, DO1
Geoffrey Smelski, PharmD1
Robert N.E. French, MD1
Michael Insel, MD2
Janet Campion MD2
1Arizona Poison and Drug Information Center and 2Division of Pulmonary, Allergy, Critical Care and Sleep
University of Arizona
Tucson, AZ USA
History of Present Illness
A 32-year-old woman with history of chronic neck pain and opioid abuse complained of dizziness and palpitations shortly before suffering a witnessed cardiac arrest in her home. She was given bystander cardiopulmonary resuscitation until emergency medical services arrived on scene, at which point intermittent polymorphic ventricular tachycardia with a pulse was noted on the cardiac monitor and physical exam (Figure 1).
Figure 1. Rhythm strips showing ventricular tachycardia (A) and a prolonged QT interval (B).
Which of the following is (are) the most likely cause(s) of the cardiac arrythmia? (Click on the correct answer to be directed to the second of seven pages)
Cite as: Watkins SA, Smelski G, French RNE, Insel M, Campion J. January 2019 critical care case of the month: A 32-year-old woman with cardiac arrest. Southwest J Pulm Crit Care. 2019;18(1):1-7. doi: https://doi.org/10.13175/swjpcc121-18 PDF
Ultrasound for Critical Care Physicians: Characteristic Findings in A Complicated Effusion
Emilio Perez Power MD, Madhav Chopra MD, Sooraj Kumar MD, Tammy Ojo MD, and James Knepler MD
Division of Pulmonary, Allergy, Critical Care and Sleep
University of Arizona College of Medicine
Tucson, AZ USA
Case Presentation
A 60-year-old man with right sided invasive Stage IIB squamous lung carcinoma, presented with a one week history of progressively worsening shortness of breath, fever, and chills. On admission, the patient was hemodynamically stable on 5L nasal cannula with an oxygen saturation at 90%. Physical exam was significant for a cachectic male in moderate respiratory distress using accessory muscles but able to speak in full sentences. His pulmonary exam was significant for severely reduced breath sound on the right along with dullness to percussion. His initial laboratory finding showed a mildly elevated WBC count 15.3 K/mm3, which was neutrophil predominant and initial chest x-ray with complete opacification of the right hemithorax. An ultrasound of the right chest was performed (Figure 1).
Figure 1. Ultrasound of the right chest, mid axillary line, coronal view.
Based on the ultrasound image shown what is the likely cause of the patient’s opacified right hemithorax?
Cite as: Power EP, Chopra M, Kumar S, Ojo T, Knepler J. Ultrasound for critical care physicians: characteristic findings in a complicated effusion. Southwest J Pulm Crit Care. 2018;17(6):150-2. doi: https://doi.org/10.13175/swjpcc122-18 PDF
October 2018 Critical Care Case of the Month: A Pain in the Neck
Robert A. Raschke, MD
Critical Care Medicine
HonorHealth Scottsdale Osborn Medical Center
Scottsdale, AZ USA
History of Present Illness
A 54-year-old man was admitted after he had a decline in mental status. He complained of neck and back pain for one week prior to admission for which he took acetaminophen. He was seen in the emergency department two days prior to admission and diagnosed with “arthritis” and prescribed oxycodone/acetaminophen and cyclobenzaprine. On the day of admission be became unresponsive and was transported by ambulance to the emergency department where he was intubated for airway protection.
Past Medical History, Social History, Family History
- Alcoholism
- Hepatitis C
- Esophageal varices
- Family history is noncontributory
Physical Examination
- Vitals: T 102° F, BP 150/60 mm Hg, P 114 beats/min, 20 breaths/min
- Unresponsive
- Dupuytren’s contractures, spider angiomata
- 3/6 systolic murmur
- Deep tendon reflexes 3+
- Bilateral Babinski’s sign (toes upgoing)
Which of the following are diagnostic considerations at this time? (Click on the correct answer to be directed to the second of six pages)
Cite as: Raschke RA. October 2018 critical care case of the month: a pain in the neck. Southwest J Pulm Crit Care. 2018;17(4):108-13. doi: https://doi.org/10.13175/swjpcc098-18 PDF
August 2018 Critical Care Case of the Month
Emma Simpson, MD
Banner University Medical Center Phoenix
Phoenix, AZ USA
History of Present Illness
A 19-year-old gravida 1, para 0 woman in her early second trimester presented to the Emergency Department with intractable vomiting, green sputum icteric sclerae, chest pain, palpitations and weakness for one week prior to presentation. She was visiting the US from an island in Micronesia. The patient has been experiencing feelings of general malaise since the beginning of her pregnancy: she experienced severe nausea and vomiting throughout her first trimester, and a 4.5 kg weight loss in the 2 months prior to presentation.
PMH, SH, FH
Before becoming pregnant, the patient was active and healthy. She does not smoke and her family history is unremarkable.
Physical Examination
Physical exam showed a thin, small young woman. Her physical examination showed a tachycardia of 114 and icteric sclera but was otherwise unremarkable.
Which of the following should be done? (Click on the correct answer to proceed to the second of six pages)
- Admit to the hospital with measurement of electrolytes, transaminases and bilirubin
- Discharge to home with a prescription for pyridoxine/doxylamine
- Ultrasound
- 1 and 3
- All of the above
Cite as: Simpson E. August 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;17(2):53-8. doi: https://doi.org/10.13175/swjpcc092-18 PDF
March 2018 Critical Care Case of the Month
Babitha Bijin MD
Jonathan Callaway MD
Janet Campion MD
University of Arizona
Department of Medicine
Tucson, AZ USA
Chief Complaints
- Shortness of breath
- Worsening bilateral LE edema
History of Present Illness
A 53-year-old man with history of multiple myeloma and congestive heart failure presented to the emergency department with complaints of worsening shortness of breath and bilateral lower extremity edema for last 24 hours. In the last week, he has had dyspnea at rest as well as a productive cough with yellow sputum. He describes generalized malaise, loss of appetite, possible fever and notes new bilateral pitting edema below his knees. Per patient, he had flu-like symptoms one week ago and was treated empirically with oseltamivir.
Past Medical History
- Multiple myeloma-IgG kappa with calvarial and humeral metastases, ongoing treatment with cyclophosphamide, bortezomib and dexamethasone
- Community acquired pneumonia 2016, treated with oral antibiotics
- Heart failure with echo 10/2017 showing moderate concentric left ventricular hypertrophy, left ventricular ejection fraction 63%, borderline left atrial and right atrial dilatation, diastolic dysfunction, right ventricular systolic pressure estimated 25 mm Hg
- Hyperlipidemia
- Chronic kidney disease, stage III
Home Medications: Aspirin 81mg daily, atorvastatin 80mg daily, furosemide 10mg daily, calcium / Vitamin D supplement daily, oxycodone 5mg PRN, chemotherapy as above
Allergies: No known drug allergies
Social History:
- Construction worker, not currently working due to recent myeloma diagnosis
- Smoked one pack per day since age 16, recently quit with 30 pack-year history
- Drinks beer socially on weekends
- Married with 3 children
Family History: Mother with hypertension, uncle with multiple myeloma, daughter with rheumatoid arthritis
Review of Systems: Negative except per HPI
Physical Exam
- Vitals: T 39.3º C, BP 80/52, P121, R16, SpO2 93% on 2L
- General: Alert man, mildly dyspneic with speech
- Mouth: Nonicteric, moist oral mucosa, no oral erythema or exudates
- Neck: No cervical neck LAD but JVP to angle of jaw at 45 degrees
- Lungs: Bibasilar crackles with right basilar rhonchi, no wheezing
- Heart: Regular S1 and S2, tachycardic, no appreciable murmur or right ventricular heave
- Abdomen: Soft, normal active bowel sounds, no tendernesses, no hepatosplenomegaly
- Ext: Pitting edema to knees bilaterally, no cyanosis or clubbing, normal muscle bulk
- Neurologic: No focal abnormalities on neurologic exam
Laboratory Evaluation
- Complete blood count: WBC 15.9 (92% neutrophils), Hgb/Hct 8.8/27.1, Platelets 227
- Electrolytes: Na+ 129, K+ 4.0, Cl- 100, CO2 18, blood urea nitrogen 42, creatinine 1.99 (baseline Cr 1.55)
- Liver: AST 35, ALT 46, total bilirubin1.7, alkaline phosphatase 237, total protein 7.4, albumin 2.
- Others: troponin 0.64, brain naturetic peptide 4569, venous lactate 2.6
Chest X-ray
Figure 1. Admission chest x-ray.
Thoracic CT (2 views)
Figure 2. Representative images from the thoracic CT scan in lung windows.
What is most likely etiology of CXR and thoracic CT findings? (Click on the correct answer to proceed to the second of seven pages)
- Coccidioidomycosis pneumonia
- Pulmonary edema
- Pulmonary embolism with infarcts
- Staphylococcus aureus pneumonia
- Streptococcus pneumoniae infection
Cite as: Bijin B, Callaway J, Campion J. March 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;16(3):117-25. doi: https://doi.org/10.13175/swjpcc035-18 PDF
January 2018 Critical Care Case of the Month
Theodore Loftsgard, APRN, ACNP
Department of Anesthesiology and Critical Care
Mayo Clinic Minnesota
Rochester, MN USA
History of Present Illness
The patient is a 51-year-old woman admitted with a long history of progressive shortness of breath. She has a long history of “heart problems”. She uses supplemental oxygen at 1 LPM by nasal cannula.
Past Medical History, Social History and Family History
She also has several comorbidities including renal failure with two renal transplants and a history of relatively recent RSV and CMV pneumonia. She is a life-long nonsmoker. Her family history is noncontributory.
Physical Examination
- Vital signs: Blood pressure 145/80 mm Hg, heart rate 59 beats/min, respiratory rate 18, T 37.0º C, SpO2 91% of 1 LPM.
- Lungs: Clear.
- Heart: Regular rhythm with G 3/6 systolic ejection murmur at the base.
- Abdomen: unremarkable.
- Extremities: no edema
Which of the following should be performed? (Click on the correct answer to proceed to the second of seven pages)
Cite as: Loftsgard T. January 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;16(1):1-7. doi: https://doi.org/10.13175/swjpcc155-17 PDF
November 2017 Critical Care Case of the Month
Stephanie Fountain, MD
Pulmonary and Critical Care Medicine
Banner University Medical Center Phoenix
Phoenix, AZ USA
History of Present Illness
A 56-year-old man presented with “food stuck in throat” since eating steak 18 hours prior to presentation. He is unable to eat or drink and has a sore throat. He is able to speak but has a “hoarse voice.” He denied drooling.
Past Medical History, Family History, and Social History
- He described himself as “healthy” and had not sought medical care in years.
- Former smoker but quit 2 years ago.
- He uses alcohol daily.
- He denied illicit drug use.
Physical Exam
- Afebrile, blood pressure 137/74 mm HG, heart rate 74 beats/min, SpO2 98% on room air.
- Physical exam was normal
Which of the following should be done next? (Click on the correct answer to proceed to the second of six pages)
- Esophagogastroduodenoscopy (EGD)
- Papain (Adolph’s Meat Tenderizer®) administration
- Tracheostomy
- 1 and 3
- All of the above
Cite as: Fountain S. November 2017 critical care case of the month. Southwest J Pulm Crit Care. 2017;15(5):191-8. doi: https://doi.org/10.13175/swjpcc130-17 PDF
ACE Inhibitor Related Angioedema: A Case Report and Brief Review
F. Brian Boudi, J. L. Rush, Cameron Farsar, Connie S. Chan
Carl T. Hayden VA Medical Center
University of Arizona, College of Medicine Phoenix Campus
Phoenix, AZ USA
Abstract
We present a case report of angiotensin converting enzyme (ACE) inhibitor angioedema successfully treated with icatibant (Firazyr®). The pathophysiology and treatment of ACE inhibitor angioedema is reviewed.
Introduction
Angioedema, swelling caused by a rapid increase in permeability of submucosal or subcutaneous capillaries and post-capillary venules with localized plasma extravasation, is associated with random, highly variable and often unpredictable clinical manifestations (1). Attacks are associated with significant decreased quality of life both during and between attacks, significant functional impairment and a high risk of morbidity and mortality. Angioedema can be caused by either mast cell degranulation or activation of the kallikrein-kinin cascade. ACE inhibitor-related angioedema is one the leading causes of drug-induced angioedema. While ACE inhibitor-induced angioedema is rare, awareness of this serious and potentially life-threatening complication is of great importance because of the extensive use of this class of drugs in clinical practice. Cases presenting into the emergency department because ACE inhibitors, one of the most widely prescribed medications prescribed in the United States, account for about 20-40 percent of emergency room admissions related to angioedema (1,2).
Approximately 50% of patients with ACE inhibitor-induced angioedema arise within the first week of treatment. The remainder can become symptomatic weeks, months, or even years later. The estimated incidence is likely underestimated. The actual incidence can be far higher because of poorly recognized presentation of angioedema and its sometimes-late onset. The incidence can be even higher (up to 3-fold) in certain risk groups, for instance Afro-Americans (3). It seems to have a predilection for the head, neck, lips, mouth, tongue, larynx, pharynx, and subglottal areas without urticaria (4).
Case Presentation
A 55-year-old veteran presented to the Emergency Department for the Carl T. Hayden Veterans Administration Medical Center in Phoenix Arizona with impressive angioedema. The Veteran had been taking lisinopril for 6 years and had another similar episode two months prior. The prior episode presented with facial swelling that resolved within a couple of hours. However, the present episode was accompanied by difficulty breathing and swallowing. He was begun on an allergic reaction protocol which included establishing and making sure the veteran had a patent airway, nasal trumpet, placing a peripheral intravenous catheter and starting iv fluid of sodium chloride 0.9% to keep vein open, medications of diphenhydramine 50 mg, famotidine 20 mg, methylprednisolone 125mg and 0.3 mg epinephrine subcutaneously. He was also given racemic epinephrine mixed via nebulizer and 30 mg subcutaneously of icatibant (Firazyr®), a bradykinin B2 receptor antagonist used to treat hereditary angioedema. He improved and was subsequently admitted to the intensive care unit for continued observation. The following day he was discharged with prescriptions for prednisone and orders to discontinue the use of lisinopril.
Discussion
Despite newer therapies, there are no currently approved guidelines for the treatment of ACE inhibitor-induced angioedema in the United States. It is difficult to tell whether icatibant was truly effective in this case presentation as it was one of multiple therapies administered. Many causes of angioedema result from release of histamine (1). However, ACE inhibitor angioedema results from other inflammatory mediators, especially bradykinin (2) (Figure 1).
Figure 1. Simplified pathway for bradykinin-mediated angioedema showing the sites of drug activity (5).
Mast cells are not believed to be involved in this form of angioedema, and pruritus and urticaria are absent. Bradykinin-mediated angioedema, unlike histamine-mediated angioedema, frequently affects the gastrointestinal mucosa, leading to bowel wall edema and presenting with episodes of abdominal pain, nausea, vomiting, and/or diarrhea. While antihistamines and corticosteroids are often administered for treatment of angioedema, they are unlikely to have effect in ACE inhibitor induced angioedema. Epinephrine may slow (or stop) the rate of swelling. ACE inhibitor angioedema may be treated with additional drugs that act on the bradykinin pathway (e.g., icatibant, ecallantide). The recommended dose of icatibant is 30 mg administered by subcutaneous (SC) injection in the abdominal area. Additional doses may be administered in 6 hours if response is inadequate. Icatibant may decrease the time of recovery from ACE inhibitor related angioedema (6). Another ACE inhibitor should not be prescribed as the reaction is a class, not a drug specific reaction (7). Checking the complement C4 may be helpful. Patients with preexisting angioedema, including hereditary angioedema caused by C1 esterase inhibitor deficiency, are predisposed to develop angioedema in response to ACE inhibitors (8).
ACE inhibitor induced angioedema remains a disorder without a clear treatment modality for reduction of symptoms. The primary therapeutic interventions remain removal of the offending agent and airway management when indicated. The use of icatibant may be effective in the management of ACE inhibitor related angioedema; however, its efficacy and benefits have not been clear in the small studies published thus far. There have been three randomized trials evaluating the use of icatibant in ACE inhibitor angioedema. Interestingly, the first study found icatibant to be effective while the more recent and larger studies found no significant difference in time to recovery (3, 6, 9-12). Icatibant is costly with a wholesale price of $9,000-$11,000 and may not be available at all hospitals. Given its questionable outcomes data, icatibant may not appropriate in all medical centers. This is especially important since off-label use may not be covered by insurers.
References
- Stone C Jr, Brown NJ. Angiotensin-converting enzyme inhibitor and other drug-associated angioedema. Immunol Allergy Clin North Am. 2017 Aug;37(3):483-495. [CrossRef] [PubMed]
- Guyer AC, Banerji A. ACE inhibitor-induced angioedema. UpToDate. June 27, 2017. Available at: https://www.uptodate.com/contents/an-overview-of-angioedema-clinical-features-diagnosis-and-management#H30 (requires subscription, accessed 9/18/17).
- Straka BT, Ramirez CE, Byrd JB, et al. Effect of bradykinin receptor antagonism on ACE inhibitor-associated angioedema. J Allergy Clin Immunol. 2017;140:242-248.e2. [CrossRef] [PubMed]
- Sabroe R, Black A. Angiotensin-converting enzyme (ACE) inhibitors and angio-oedema. Br J Dermatol. 1997;1:153–8. [CrossRef] [PubMed]
- Shenvi C, Serrano K. New treatments for angioedema. Emergency Physicians Monthly. 9/12/16. Available at: http://epmonthly.com/article/new-treatments-angioedema/ (accessed 10/20/17).
- Baş M, Greve J, Stelter K, et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015 Jan 29;372(5):418-25. [CrossRef] [PubMed]
- Johnsen SP, Jacobsen J, Monster TB, Friis S, McLaughlin JK, Sørensen HT.Risk of first-time hospitalization for angioedema among users of ACE inhibitors and angiotensin receptor antagonists. Am J Med. 2005;1:1428-9. [CrossRef] [PubMed]
- Orfan N, Patterson R, Dykewicz M. Severe angioedema related to ACE inhibitors in patients with a history of idiopathic angioedema. JAMA. 1990;1:1287-9. [CrossRef] [PubMed]
- Sinert R, Levy P, Bernstein JA, et al.Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1402-9.e3. [CrossRef] [PubMed]
- Culley CM, DiBridge JN, Wilson GL Jr. Off-label use of agents for management of serious or life-threatening angiotensin converting enzyme inhibitor-induced angioedema. Ann Pharmacother. 2016 Jan;50(1):47-59 [CrossRef] [PubMed]
- Fok JS, Katelaris CH, Brown AF, Smith WB. Icatibant in angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. Intern Med J. 2015 Aug;45(8):821-7. [CrossRef] [PubMed]
- Riha HM, Summers BB, Rivera JV, Van Berkel MA. Novel therapies for angiotensin-converting enzyme inhibitor-induced angioedema: a systematic review of current evidence. J Emerg Med. 2017 Sep 19. pii: S0736-4679(17)30489-4. [CrossRef] [PubMed]
Cite as: Boudi FB, Rush JL, Farsar C, Chan CS. ACE inhibitor related angioedema: a case report and brief review. Southwest J Pulm Crit Care. 2017;15(4):165-8. doi: https://doi.org/10.13175/swjpcc114-17 PDF
Tumor Lysis Syndrome from a Solitary Nonseminomatous Germ Cell Tumor
Brandon T. Nokes, MD1
Rodrigo Cartin-Ceba, MD2
Joseph Farmer, MD2
Alyssa B. Chapital, MD, PhD2
1Hospital Internal Medicine and 2Division of Critical Care
Mayo Clinic Arizona
Phoenix, AZ USA
Abstract
Spontaneous tumor lysis syndrome is a rare clinical entity, which typically occurs in the context of rapidly proliferating hematologic malignancies. Tumor lysis syndrome in solid organ malignancies is even rarer, and typically provoked by cytotoxic treatment regimens. We describe a case of spontaneous tumor lysis of a solitary metastatic brain lesion from a nonseminomatous germ cell tumor. This case is unique in that spontaneous tumor lysis from a brain metastasis of a solid organ malignancy has never been reported, and spontaneous tumor lysis in a nonseminomatous germ cell tumor is exceedingly rare.
Case Report
A 31-year-old gentleman was admitted to our facility after developing status epilepticus and consequently, being involved in a MVA. Imaging revealed a 3.5cm right frontal brain lesion with surrounding edema, but no other acute intracranial pathology. The patient was intubated, sedated, and transferred to critical care for further treatment. His past medical history was notable for primary surgical resection of a T1N0M0 nonseminomatous germ cell tumor in March 2015, followed by detection of a 2.5cm lung nodule in September 2015, with concurrent beta-human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) biochemical recurrence. He underwent 4 cycles of bleomycin, etoposide, and cisplatin (BEP).
A head CT revealed a 4cm x 3.5cm right frontal lesion with surrounding edema (Figure 1).
Figure 1. T2 Axial MRI showing 4 cm x 3.5 cm lesion with associated vasogenic edema.
Dexamethasone 4mg every 6 hours was initiated for treatment of vasogenic edema. Laboratory studies were significant for a white blood cell count elevated at 19.3 x109/L, international normalized ratio (INR) 1.34, partial thromboplastin time (PTT) 26.2 seconds, and prothrombin time (PT) 16.1 seconds. Plasma lactate was elevated at 30.6mmol/L. Bicarbonate was 6mmol/L with an anion gap of 45, glucose 186mg/dL, BUN 15.2mg/dL, and creatinine was 2.0mg/dL. Urine drug screen was negative. His AFP was 7.4ng/mL and beta-HCG was 13IU/L. Over the following 24 hours, the patient experienced decreased urine output. A bedside ultrasound reveals normal IVC collapse. Further lab assessment revealed a CK within normal limits and a urinalysis showed the presence of 11 to 20 RBCs, 4 to 10 WBCs and some granular casts as well as trace protein. His phosphorus was 8.9, calcium 8.1, and uric acid was 13mg/dL. His lactate dehydrogenase levels were also elevated at 271 U/L.
Due to concern of tumor lysis syndrome, the patient was initiated on rasburicase, which was followed by maintenance allopurinol 300mg daily. However, due to worsening renal failure, the patient was started on hemodialysis. He was taken to the operating room the following morning for immediate surgical resection of his brain metastasis; no evidence of residual disease was seen on follow-up imaging (Figure 2).
Figure 2. T2 Axial MRI status post a right frontal craniotomy and gross total resection of the previously noted mass. Small amount of blood noted within the resection cavity. Residual vasogenic edema persists in the white matter surrounding the operative bed.
Repeat chest, abdomen and pelvis imaging did not show any additional metastatic lesions.
In the following days, he was subsequently extubated, transferred to the floor, and continued hemodialysis, eventually fully recovering his renal function. Ultimately, he was discharged with outpatient follow-up for additional chemotherapy planning after physical rehabilitation.
Discussion
Tumor lysis syndrome (TLS) can be subdivided into laboratory TLS and clinical TLS, as defined by the Cairo-Bishop diagnostic criteria (1). Spontaneous TLS can occur in solid organ malignancies (1). TLS in solid organ malignancies is provoked by chemotherapy or radiation therapy, which creates massive cell lysis and elaboration of intracellular potassium, phosphate, and uric acid as well as hypocalcemia, which can lead to renal failure and cardiac dysrhythmias (1). LDH is also elevated. TLS can also be thought of as being provoked, either by ongoing chemotherapy or a decrease in effective circulating volume, or unprovoked. It is rare for TLS to occur in nonseminomatous germ cell tumors. Only 2 case reports have been published regarding spontaneous TLS in nonseminomatous germ cell tumors (2,3). Our case is most likely a spontaneous TLS. To date, no reports have been published regarding spontaneous TLS from a solitary brain metastasis from a nonseminomatous germ cell tumor. Further, no cases have been reported regarding tumor lysis from a solitary brain metastasis of any solid organ malignancy.
The occurrence of TLS in solid organ malignancies is thought to occur secondary to rapid cellular proliferation that exceeds the available blood supply for a tumor, leading to tumor ischemia and diffuse tumor cell necrosis. The biochemical milieu elaborated from these necrotic cells can result in end-organ pathology.
The treatment of TLS is contingent upon the rate of cancer progression and whether there is evidence of end-organ damage. Importantly and ideally, patients can be stratified into intermediate, moderate, or high-risk of developing TLS based on their malignancy type and rate of cancer progression, such that TLS may be prevented with prophylactic hydration, electrolyte monitoring and allopurinol or rasburicase (4,5). Biochemical TLS alone can be treated with IV hydration and allopurinol, a xanthine oxidase inhibitor which potentially halts TLS progression. When there is end-organ damage, rasburicase (a recombinant urate oxidase) is the first-line treatment along with aggressive hydration (5). Additional therapies are directed towards minimizing sequelae of TLS (i.e. calcium gluconate for hyperkalemia associated EKG changes or emergent dialysis for acute renal failure). There is no role for urinary alkalinization.
We were fortunate in that our patient had a great outcome, owing to early detection and aggressive intervention, and we implore our fellow physicians to be mindful of TLS as a possible clinical outcome in all malignancies, irrespective of its clinical rarity.
References
- Mirrakhimov AE, Ali AM, Khan M, Barbaryan A. Tumor lysis syndrome in solid tumors: an up to date review of the literature. Rare Tumors. 2014;6(2):5389. [CrossRef] [PubMed]
- D'Alessandro V, Greco A, Clemente C, et al. Severe spontaneous acute tumor lysis syndrome and hypoglycemia in patient with germ cell tumor. Tumori. 2010;96(6):1040-3. [PubMed]
- Pentheroudakis G, O'Neill VJ, Vasey P, Kaye SB. Spontaneous acute tumour lysis syndrome in patients with metastatic germ cell tumours. Report of two cases. Support Care Cancer. 2001;9(7):554-7. [CrossRef] [PubMed]
- Feres GA, Salluh JI, Ferreira CG, Soares M. Severe acute tumor lysis syndrome in patients with germ-cell tumors. Indian J Urol. 2008;24(4):555-7. [CrossRef] [PubMed]
- Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol. 2008;26(16): 2767-78. [CrossRef] [PubMed]
Cite as: Nokes BT, Cartin-Ceba R, Farmer J, Chapital AB. Tumor lysis syndrome from a solitary nonseminomatous germ cell tumor. Southwest J Pulm Crit Care. 2017;15(4):148-50. doi: https://doi.org/10.13175/swjpcc107-17 PDF
October 2017 Critical Care Case of the Month
Margaret Ragland, MD1
Carolyn H. Welsh, MD1,2
Pulmonary Sciences and Critical Care Medicine
1University of Colorado Anschutz Medical Campus and 2VA Eastern Colorado Health Care System
Denver, Colorado USA
History of Present Illness
A 42-year-old man with a history of intravenous heroin abuse and chronic hepatitis C infection presents to the emergency department (ED) with recurrent abdominal pain. The pain was dull, epigastric, and did not radiate. The pain worsened after eating, but the timing after eating that it worsened was inconsistent. He had nausea but no vomiting. His bowel movements were normal without constipation, diarrhea, or melena.
He had presented to another ED multiple times with this same pain over the past six weeks. He does not know what the work-ups revealed, but was discharged from the emergency department each time. He received supportive care including fluids and analgesics, but the pain would always recur a few hours after returning home.
He went to a third ED a few weeks ago with bilateral testicular pain after which he was discharged home with acetaminophen for pain.
Past Medical History, Family History, and Social History
His past medical history is notable for bipolar disorder. He takes no prescribed medications and does not know his family’s medical history. He is a current every day smoker, has no history of heavy alcohol use, and uses intravenous heroin but no other recreational drugs.
Current Medications
Acetaminophen a few times a day for abdominal pain.
Review of Systems
He notes subjective fevers, poor appetite, and an 8 pound unintentional weight loss over the past six weeks.
Physical Exam
Vital signs are notable for hypertension to 158/91 mm Hg. Other vitals are within normal limits.
On exam, he is an ill appearing middle aged man who appears very uncomfortable. His abdomen is nondistended. He has normal bowel sounds and epigastric tenderness with a tender, smooth liver edge palpable just under the costal margin. He has decreased sensation to light touch in his toes with no skin changes. Toes are warm with capillary refill less than two seconds.
Laboratory Evaluation
CBC reveals a leukocytosis to 23,600 cells/mcL with 80% neutrophils; eosinophils are normal. Hemoglobin and platelet counts are normal. Sodium is 128 mmol/L with a bicarbonate of 30 mmol/L and creatinine of 0.64 mmol/L. AST 155 U/L, ALT 137 U/L, with a total bilirubin 1.1 mmol/L. Albumin is 1.8 g/L. INR is 1.9. Urinalysis showed 1+ protein.
What additional laboratory evaluation is indicated at this time? (Click on the correct answer to proceed to the second of six pages)
Cite as: Ragland M, Welsh CH. October 2017 critical care case of the month. Southwest J Pulm Crit Care. 2017;15(4):131-7. doi: https://doi.org/10.13175/swjpcc113-17 PDF
September 2017 Critical Care Case of the Month
James T. Dean III, MD
Tyler R. Shackelford, DO
Michel Boivin, MD
Division of Pulmonary, Critical Care and Sleep Medicine
University of New Mexico School of Medicine
Albuquerque, NM USA
Critical Care Case of the Month CME Information
Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity.
0.25 AMA PRA Category 1 Credit(s)™
Estimated time to complete this activity: 0.25 hours
Lead Author(s): James T. Dean III, MD. All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.
Learning Objectives: As a result of completing this activity, participants will be better able to:
- Interpret and identify clinical practices supported by the highest quality available evidence.
- Establish the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
- Translate the most current clinical information into the delivery of high quality care for patients.
- Integrate new treatment options for patients with pulmonary, critical care and sleep related disorders.
Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.
CME Sponsor: University of Arizona College of Medicine
Current Approval Period: January 1, 2017-December 31, 2018
Financial Support Received: None
A 73-year-old man presented with a three-day history of diffuse abdominal pain, decreased urine output, nausea and vomiting. His past medical history included diabetes, coronary artery disease, hypertension and chronic back pain. The patient reported being started on hydrochlorothiazide, furosemide, pregabalin and diclofenac within the last week in addition to his long-standing metformin prescription.
Initial vitals were significant for tachypnea, tachycardia to 120 bpm, hypothermia to 35ºC and hypotension with a blood pressure of 70/40 mm Hg. Physical exam was remarkable for bilateral lung wheezing and significant respiratory distress. Laboratory examination was concerning for a pH of 6.85, pCO2 of < 5mmHg, serum lactate of 27mmol/l, WBC of 15.6 x106 cells/cc and a serum creatinine of 8.36 mg/dl. A chest X-ray showed evidence of mild pulmonary edema and a CT of the abdomen did not show any acute pathology.
What is the most likely etiology of the patient’s severe acidosis? (Click on the correct answer to proceed to the second of four pages)
Cite as: Dean JT III, Shackelford TR, Boivin M. September 2017 critical care case of the month. Southwest J Pulm Crit Care. 2017;15(3):100-3. doi: https://doi.org/10.13175/swjpcc101-17 PDF
Carotid Cavernous Fistula: A Case Study and Review
Iaswarya Ganapathiraju, OMS-IV1
Douglas T Summerfield, MD2
Melissa M Summerfield, MD2
1Des Moines University College of Osteopathic Medicine
Des Moines, IA USA
2Mercy Medical Center North Iowa and North Iowa Eye Clinic
Mason City, IA USA
Abstract
Carotid cavernous fistulas are rare complications of craniofacial trauma, resulting in abnormal connections between the arterial and venous systems of the cranium. The diagnosis of carotid cavernous fistulas and other injuries as a result of trauma can be confounded by the traumatized patient’s inability to communicate their symptoms to their physician. The following case study demonstrates the importance of a thorough physical exam in caring for such patients and serves to remind physicians to have a low threshold for consultation when managing numerous injuries following trauma.
Introduction
Carotid cavernous fistulas (CCFs) are aberrant connections between the carotid arterial system and the cavernous sinus, which form as complications of craniofacial trauma, or are congenital or spontaneous in nature (1). They occur in up to 3.8% of patients with basilar skull fractures and are more common with middle fossa fracture (2). Prompt diagnosis and treatment of CCF is necessary as approximately 20 – 30% of carotid cavernous fistulas lead to vision loss if not addressed appropriately (3)/\The following is a case study of a patient who presented with multiple traumatic injuries including CCF with subsequent discussion of the typical presentation, diagnosis, and treatment of direct CCF.
Case Presentation
A 64-year-old woman with a therapeutic INR on Coumadin for atrial fibrillation sustained a fall down a flight of stairs. She was found unresponsive the next day by her relatives and was subsequently brought to the emergency department for evaluation. A maxillofacial CT showed a nondisplaced right maxillary wall fracture and nondisplaced zygomatic arch fracture, as well as a subtle inferotemporal orbital fracture, none of which was determined to require immediate treatment by the otolaryngology service. Further imaging included a CT of the head which revealed a large subdural hematoma, a superotemporal hematoma, and subfalcine herniation. She was taken to the OR for emergent craniotomy and evacuation of the hematoma before transfer to the critical care unit. In the CCU, she remained intubated and sedated but her condition improved until extubation on hospital day 3. She continued to have swelling surrounding both eyes during this time, but physical exam showed pupils which were equal, round, and reactive to light.
On day 6 of her stay, the patient was noted to have waxing and waning confusion and slightly increased oxygen requirement. Thus, she was re-intubated and sedated for “agitation” and “hypoxic respiratory failure.” Physical exam on the next day was notable for pupillary anisocoria with the right pupil at 1 mm diameter and left at 2.5 mm. There was a poor pupillary light reaction bilaterally. Neurology was consulted and recommended repeat imaging and EEG. Repeat CT and MRI of the brain showed no evidence of herniation, and EEG was negative for seizure-like activity. The anisocoria was thought to be from mass effect of the temporal lobe on cranial nerve III. The patient’s condition continued to deteriorate; physical exam elicited grimace to painful stimuli and the patient was able to open her eyes but did not track movement or follow commands. She was subsequently noted to have a left orbit that became harder to compress with ballottement test compared to the right, so Ophthalmology was consulted.
An ophthalmologic exam showed extensive chemosis of the left eye compared to the right with conjunctival hemorrhage in bilateral eyes (Figure 1).
Figure 1. Ophthalmologic exam revealed chemosis, exophthalmos, and a mid-dilated, fixed pupil of left eye compared to right.
Ocular tonometry revealed a pressure of 14 mmHg in the right eye and 53 mmHg in the left. There was a mid-dilated, fixed pupil on the left. The differential at this point included traumatic acute angle closure glaucoma versus a retroorbital process. The patient was started on timolol, pilocarpine, and dorzolamide eye drops for intraocular pressure control. An orbital CT was obtained, which showed an engorged superior ophthalmic vein on the left with a new 4 mm proptosis of the left eye (Figure 2) when compared to previous imaging.
Figure 2. A: CT scan showed proptosis of 4 mm of left eye compared to right eye. B: Enlarged left ophthalmic vein also noted on CT scan (arrow).
This raised concern for traumatic carotid cavernous fistula. A CTA obtained the following morning confirmed this suspicion (Figure 3).
Figure 3. A: Reconstructed coronal CT coronal angiogram showing enlarged left cavernous sinus, confirming diagnosis of carotid cavernous fistula. B-E: Static coronal images from CT angiogram with major arteries labeled. F: Video of CT angiogram.
The patient was transferred to an outside facility for surgical management, which consisted of angiography and embolization via coiling of her CCF.
Discussion
Carotid cavernous fistulas are abnormal connections that form between the cavernous sinus and the internal or external carotid arteries, or branches of the internal or external carotid arteries. They are divided into direct and indirect variants per Barrow classification (Table 1, Figure 4).
ICA = Internal carotid artery ECA = External carotid artery
Figure 4. A: The normal eye: superior ophthalmic vein draining into cavernous sinus and internal and external carotid arteries traversing the cavernous sinus. B: Barrow Classifications for types of carotid cavernous fistulas: Type A: direct connection between internal carotid artery and cavernous sinus. Type B: connection between dural branches of internal carotid artery and cavernous sinus. Type C: connection between dural branches of external carotid artery and cavernous sinus. Type D: connection between dural branches of both internal carotid artery and external carotid artery and the cavernous sinus.
Types B through D are commonly termed ‘indirect’ or ‘dural’ fistulas. These can develop spontaneously as a result of hypertension and are the more common presentation of CCF. More specifically, type B is a connection between the dural branches of the ICA and the cavernous sinus, type C is a connection between the dural branches of the external carotid artery (ECA) and the cavernous sinus, and type D connects the dural supply of both the ICA and ECA and the cavernous sinus (1). Type A, or a ‘direct’ CCF, is a connection between the intracavernous internal carotid artery (ICA) and the cavernous sinus. Direct CCF is a rare ocular complication that forms most commonly as a result of craniofacial trauma, but can also be due to aneurysmal rupture or spontaneous development. This is also the most dramatic presentation of CCF and was the case in our patient.
Prompt identification and management of CCF is necessary to prevent associated morbidity and mortality. The presentation of CCF depends mainly on the drainage of the fistula. Anterior-drainage of fistulas through the superior ophthalmic vein produces symptoms of exophthalmos, proptosis, acute chemosis or swelling/edema of conjunctiva, and headache, all of which are more common in direct CCFs. The backup of drainage can result in a secondary angle closure with extremely high intraocular pressure. Posterior-drainage of fistulas into the superior and inferior petrosal sinuses tend to lack the aforementioned features of orbital congestion, but can produce painful cranial neuropathy of the trigeminal, facial, or ocular motor nerves. Failure to identify and appropriately treat posterior-draining fistulas can lead to eventual reversal of flow and development of anterior drainage (4).
The signs of CCF are not visible on neuroimaging at a patient’s presentation and generally develop over the first week a patient is admitted. Clinical signs which may prompt further investigation and repeat imaging include chemosis, increasing exophthalmos, pain, and increased intraocular pressure. Often, the tools for checking intraocular pressure are not available in an ICU setting. In the absence of signs of a ruptured globe, an intensivist could palpate the orbit over a closed eye (as occurred in this case). If there is asymmetry in resistance to palpation, this should incite an ophthalmologic consult to consider a retro-orbital process.
Repeat neuroimaging is likely to be done in these cases, but it is important to order the right test. Radiologic signs of CCF include proptosis and asymmetric enlargement of a cavernous sinus or superior ophthalmic vein and would be noted on an orbital or maxillofacial CT. A head CT might miss these signs, so it is important to obtain imaging dedicated to examining the retro-orbital space. To confirm the diagnosis of CCF, one must then obtain a CT angiogram, which will show the aberrant connections between the intracranial vessels. Upon confirming a diagnosis of CCF, the preferred mode of management is endovascular obliteration using an arterial or venous approach as it has been shown to be safe and effective, and confers long-term cure in most cases (5).
A previous review of 16 cases of carotid cavernous fistulas treated with transarterial embolization with detachable balloon show satisfactory results, defined as resolution of CCF without residual disability, in 11 cases and resolution but with residual disability in 5 cases. The most common of the disabilities in these cases was vision impairment, as seen in 4 out of the 5 cases. In addition, 14 out of the 16 cases resolved with preserved internal carotid artery flow (1). As a result, transarterial embolization with detachable balloon (TAEDB) has been established as the preferred method of treatment for carotid cavernous fistulas (6). Other options for treatment include neurosurgery and stereotactic radiosurgery when endovascular approach is not feasible.
Our patient presented with several traumatic injuries following a fall down a flight of stairs and was unable to contribute to history-taking. Detection and treatment of the CCF that she later developed was complicated by several factors. The true exophthalmos of the affected eye was partially masked by the fact that she had an inferotemporal orbital fracture of the opposite eye, which was incorrectly thought to be enophthalmic. Additionally, her altered mental status and subsequent re-intubation limited her ability to vocalize the pain which would have been present in her affected eye due to tremendously increased intraocular pressure.
From a critical care physician perspective, part of the key to her diagnosis was her re-intubation. The patient developed severe agitation requiring sedation without other more typical reasons for intubation such as hypoxia, tachypnea, or dyssynchronous breathing. We suspect this agitation was likely secondary to pain from the rapidly increasing pressure in her affected eye which became symptomatic just prior to her worsening mental status. Her physical exam was ultimately crucial to the detection of her CCF, specifically chemosis, exophthalmos, and increased intraocular pressure in the affected eye. These signs led to the subsequent ophthalmologic consultation, imaging, and eventually the diagnosis of CCF.
An important lesson learned from this patient’s management is having a low threshold for consultation when the clinical picture does not match diagnostic workup. In our case, the patient’s clinical condition changed but repeat workup including EEG and MRI of the head was negative. Previous imaging had revealed right-sided facial fractures, yet her new findings, including increased resistance to palpation of the orbit and chemosis, were largely left-sided. In situations when the cause of a patient’s deteriorating condition is unclear and there is incongruity between the physical exam and diagnostic workup, it is imperative to obtain further consultation. In our case, the ophthalmic exam gave the clues for further workup and the ultimate diagnosis.
In conclusion, this patient’s case is a good study in the classic presentation of direct CCF in association with craniofacial trauma, and also illuminates the difficulty in detection of orbital injuries in a trauma patient who cannot vocalize the symptoms they are experiencing. The lesson learned from her presentation is to have a low threshold for ophthalmologic consultation for unexplained changes in ophthalmic condition and discrepancies between clinical presentation and diagnostic findings.
References
- Barrow DL, Spector RH, Braun IF, Landman JA, Tindall SC, Tindall GT. Classification and treatment of spontaneous carotid-cavernous sinus fistulas. J Neurosurg. 1985 Feb;62(2):248-56. [CrossRef] [PubMed]
- Liang W, Xiaofeng Y, Weiguo L, Wusi Q, Gang S, Xuesheng Z. Traumatic carotid cavernous fistula accompanying basilar skull fracture: a study on the incidence of traumatic carotid cavernous fistula in the patients with basilar skull fracture and the prognostic analysis about traumatic carotid cavernous fistula. J Trauma. 2007 Nov;63(5):1014-20. [CrossRef] [PubMed]
- Doran M. Carotid-Cavernous Fistulas: Prompt Diagnosis Improves Treatment. American Academy of Ophthalmology. https://www.aao.org/eyenet/article/carotid-cavernous-fistulas-prompt-diagnosis-improv. Published March 18, 2016. Accessed July 11, 2017.
- Miller NR. Diagnosis and management of dural carotid-cavernous sinus fistula. Neurosurg Focus. 2007;23(5):E13. [PubMed]
- Gupta AK, Purkayastha S, Krishnamoorthy T, Bodhey NK, Kapilamoorthy TR, Kesavadas C, Thomas B. Endovascular treatment of direct carotid cavernous fistulae: a pictorial review. Neuroradiology. 2006 Nov;48(11):831-9. [CrossRef] [PubMed]
- Lewis AI, Tomsick TA, Tew JM Jr, Lawless MA. Long-term results in direct carotid-cavernous fistulas after treatment with detachable balloons. J Neurosurg. 1996 Mar;84(3):400-4. [CrossRef] [PubMed]
Cite as: Ganapathiraju I, Summerfield DT, Summerfield MM. Carotid cavernous fistula: a case study and review. Southwest J Pulm Crit Care. 2017:15(1):32-8. doi: https://doi.org/10.13175/swjpcc083-17 PDF