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.
Management of Life Threatening Post-Partum Hemorrhage with HBOC-201 in a Jehovah’s Witness
Andrea Mytinger, DO1
Elyce Sheehan, MD1
Nathan Blue, MD2
Kendall P. Crookston, MD, PhD3
Ali I. Saeed, MD 4
1Department of Internal Medicine, 2Department of Maternal and Fetal Medicine, 3Departments of Pathology of Transfusion Medicine, and 4Divisions of Pulmonary, Sleep and Critical Care Medicine
University of New Mexico School of Medicine
Albuquerque, NM USA
Abstract
Background: Post-partum hemorrhage remains the leading cause of maternal mortality worldwide. The obstetrician and critical care physician should be aware of local alternative treatment options for symptomatic anemia secondary to post-partum hemorrhage in patients who cannot receive red blood cell transfusion. Transfusion may not be an option due to strong personal belief, lack of compatible blood, or blood shortage.
Case: A 21-year-old woman, gravida 1 para 1001, was transferred to a tertiary care center for management of severe post-partum hemorrhage (hemoglobin 4.2 g/dL). She had undergone emergent dilation and curettage followed by Bakri tamponade balloon placement at an outside facility. As a member of the Jehovah’s Witness faith, she refused red blood cell transfusion. HBOC-201, a bovine hemoglobin based oxygen carrier, was successfully used to reverse symptomatic, life-threatening anemia.
Conclusion: HBOC-201 can act as a means to reverse severe end-organ damage for patients with severe post-partum hemorrhage and should be considered when no other treatment options are available.
Teaching Points
- HBOC-210 (Hemopure®) is a bovine hemoglobin-based oxygen carrier (HBOC), used as a means to reverse severe anemia in those patients who cannot receive RBC transfusion.
- The current generation of HBOCs carry fewer side effects than their predecessors. Common side effects include transient hypertension, abdominal complaints, jaundice, elevated liver and pancreatic enzymes and decreased urine output.
- The teratogenic effects of HBOC-201 remains unknown in humans.
Introduction
Worldwide, there are an estimated 14 million pregnancy-related hemorrhages each year and 25% of maternal mortality can be attributed to post-partum hemorrhage (1). While the majority of post-partum hemorrhage leading to acute blood loss anemia is treated with red blood cell (RBC) transfusion, there remains a significant subset of patients who are unable to receive this life-saving modality. In instances where RBC transfusion is not an option due to lack of compatible blood, blood shortage, or strong patient personal beliefs, there remain alternative options for management. We report the case of a young Jehovah’s Witness who presented with symptomatic anemia secondary to severe post-partum hemorrhage, treated successfully with an experimental protocol using HBOC-201 (Hemopure®).
Case
A 21-year-old female, gravida 1 para 1001, Jehovah’s Witness was transferred to a tertiary care hospital for management of post-partum hemorrhage after spontaneous vaginal delivery at 40 weeks of gestation. The patient received 3 boluses of intravenous oxytocin, 800mcg of misoprostol and 1 dose of intramuscular (IM) carboprost trimethamine. She then underwent a dilation and curettage for presumed retained products of conception. A Bakri tamponade balloon catheter (Figure 1) was placed vaginally and the patient was transferred for a higher level of care.
Figure 1. An example illustration of the Bakri vaginal tamponade balloon, placed in the uterus in attempt to apply pressure to bleeding vessels.
Prior to delivery, the patient’s hemoglobin (Hb) and hematocrit (Hct) were initially 12.4 g/dL and 36.4 %, respectively, which decreased to 5.5 g/dL and 16.4%.
On arrival, the patient ‘s heart rate was 148 beats per minute while on 2L of oxygen. The blood pressure was 93/36 mmHg. She was pale and tired-appearing with conjunctival pallor. Her abdomen exhibited generalized mild tenderness to palpation. The Bakri balloon was in place with 100 mL of drainage noted. Laboratory results revealed Hb of 4.2 g/dL, lactate of 1.2 mmol/L and troponin I of 1.820 ng/mL. The patient refused transfusion of RBC, and the other major blood products, citing her faith. After a prolonged discussion, the patient consented to the use of HBOC-201.
The patient received 2 units of HBOC-201 along with 1,000 mg of ascorbic acid. Her Hb increased from 4.2 g/dL to 4.8 g/dL, much less than the anticipated 1 g/dL increase with each unit of HBOC-201 raising concern for ongoing hemorrhage. An ultrasound was performed which revealed ongoing bleeding from the lower uterine segment behind the balloon. Methylergonovine 0.2mg IM every 6 hours was started and the patient received two additional units of HBOC-201 however, during infusion of the second unit her oxygen requirement increased from 2L by nasal cannula to 15L high flow mask at 80% FiO2. The transfusion was stopped and a chest radiograph revealed diffuse parenchymal opacities with prominent interstitial markings and small bilateral pleural effusions suggestive if fluid overload / pulmonary edema. The patient then underwent gel foam uterine artery embolization by Interventional Radiology for definitive management.
On hospital day 2 the patient’s heart rate was 114 beats per minute and Hb was 5.2 g/dL, prompting infusion of an additional 2 units of HBOC-201. Due to continued hypoxia and radiographic evidence of fluid overload, diuretic therapy was administered. Her oxygen requirement decreased to 5L by nasal cannula, however did not improve from there despite a negative fluid balance, so a CT scan of the chest was performed which revealed significant bilateral basal atelectasis. The patient’s oxygen requirement resolved with incentive spirometry. The Bakri vaginal balloon was removed and minimal bleeding was observed.
On hospital day 3 the patient’s blood pressure increased to 176/78 mmHg. This, in the setting of proteinuria, peripheral edema and elevated aspartate aminotransferase (AST) to 104 unit/L (6-58 Unit/L) raised a suspicion for post-partum preeclampsia with severe features. Intravenous magnesium sulfate was briefly initiated for seizure prophylaxis, however it was discontinued after her blood pressure stabilized and the hypertension was attributed to a possible side effect of HBOC-201.
The patient received a total of 7.5 units of HBOC-201 over the course of 4 days in the MICU. Her troponin peaked on hospital day 2 at 2.930 ng/mL, and continued to downtrend with multiple infusions of HBOC-201. The patient’s own hematocrit began rising on hospital day 5 (Figure 2).
Figure 2. Illustration of the hemoglobin and hematocrit over the course of the patient’s hospitalization and at her first out-patient follow up visit. The arrows indicate when HBOC-201 was infused. Troponin I is also depicted on this graph to illustrate the resolution of severe end-organ damage due to the severe anemia.
The patient was transferred to the obstetrics floor on hospital day 7. In accordance with recent post-partum hemorrhage recommendations, she received 1025 mg of IV iron dextran. She was discharged home in stable condition on hospital day 8 with a Hb of 6.7 g/dL and Hct of 21%. Outpatient follow-up revealed significant improvement in anemia with a Hb of 9.2 g/dL and Hct of 30% one week after discharge.
Discussion
Acute post-partum hemorrhage leading to severe anemia remains the leading cause of maternal death worldwide (2). While the majority of post-partum hemorrhage leading to acute blood loss anemia is treated with transfusion of packed RBC or other blood products, there are certain subsets of patients who are unable to accept these products. This case demonstrates the use of a bovine hemoglobin-based oxygen carrier in a Jehovah’s Witness patient with severe post-partum hemorrhage who refused blood products. There have been multiple case reports regarding the use of HBOC-201 in severely anemic Jehovah’s Witness patients; however, there is no published report to our knowledge on the use of HBOC-201 in patients with symptomatic post-partum hemorrhage.
Hemoglobin-based oxygen carriers were developed in response to the infectious issues associated with donor RBC and in an attempt to come up with an alternative treatment in those situations where RBC transfusion was not an option. The first generation of these products was known to cause renal toxicity and coagulopathy (3,4). HBOC-201 is a second generation HBOC that is a cell-free, stroma-free, polymerized version of bovine hemoglobin. Because it contains no cell membrane, it is compatible with all blood types (no cross matching is needed). The shelf life is 36 months at room temperature (5) (no refrigeration or sophisticated supply network is needed). A number of randomized control trials have been done to evaluate HBOC-201 (and other similar products) as a potential RBC replacement. However, after infusion the short 24-hour half-life and statistical increase in adverse events associated with administration made it apparent that these HBOCs were not interchangeable with RBC for routine transfusion. While they are not interchangeable, many clinicians feel that the risk-benefit profile is favorable in severely anemic patients who cannot receive RBC. HBOC-201 is not yet approved for use in the United States, and therefore cannot be used outside of clinical trials. Several compassionate use studies are available in the United States to treat patients with life-threatening anemia when no other treatment option is available. Worldwide only a few countries have approved the use of HBOC-201 (6).
The side effect profile of the second generation HBOC’s is much preferable to that of the first (4). Reported class effects of HBOC use include hypertension, esophageal dysmotility and increased risk for myocardial infarction, all of which are related to vasoconstriction secondary to increased nitric oxide scavenging in these products (5). HBOC-201 in particular, has not been reported to increase risk of myocardial infarction. Rather, it has been reported that HBOC-201 reduces cardiac hypoxia in the setting of severe anemia (7). Mongan et al. (8) found that, while HBOC-201 causes transient systemic and pulmonary hypertension in swine, blood flow to 8 major organs, including the heart, was unchanged compared to controls. Serruys et al. (9) found no significant change in coronary blood flow and no vasoconstriction in humans pre-oxygenated with HBOC-201 prior to Percutaneous Coronary Intervention for coronary artery disease. In this case, the patient presented with troponinemia, indicating type 2 demand ischemia in the setting of severe anemia. Troponin levels began to down-trend after HBOC-201 infusion.
Common side effects of HBOC-201 in particular include transient hypertension, abdominal complaints, jaundice, elevated liver and pancreatic enzymes (10) and bovine methemoglobinemia (11). To prevent the increased oxidation of infused HBOC-201 to methemoglobin, ascorbic acid is co-administered; methemoglobin levels should be monitored and treated with methylene blue should they become significantly elevated (5).
This patient did experience increased hypoxia while receiving a unit of HBOC-201 which resulted in concern for transfusion reaction and transient discontinuation of the HBOC-201 infusion. It must be noted that HBOC-201 contains no cellular or plasma components, thus many transfusion reactions such as Transfusion Related Acute Lung Injury (TRALI) are an impossibility. HBOC-201 has been associated with volume overload; as it is a colloid this is a known complication (12). Volume overload was suspected, however, the patient did not improve with diuresis, and a chest CT revealed profound atelectasis. Given that her hypoxia greatly improved with incentive spirometry and ambulation, this was deemed unlikely to be a reaction associated with HBOC-201, but rather related to being bed-bound and critically ill.
One unit of HBOC-201 will raise serum Hb from 0.5g/dL to 2g/dL (12). One to two units of HBOC-201 are typically given for Hb levels <6 g/Dl, with additional units provided to maintain a goal Hemoglobin greater than 6g/dL (11, 12). With a half-life of 19-24 hours (5, 13), HBOC-201 must be infused regularly until the patient’s bone marrow production of RBC is sufficient, as evidenced by increases in hematocrit. It should be noted that HBOC-201 will only increase serum hemoglobin and not hematocrit; an initial decrease in hematocrit may be seen after infusion secondary to hemodilution (12).
The patient presented above experienced both transient hypertension and an increase in her serum AST, raising concern for post-partum preeclampsia. She was started on treatment for severe preeclampsia, however these affects were later attributed to the HBOC-201.
HBOC-201 is currently not recommended during pregnancy. One animal study in rats indicated that HBOC-201 infusion during organogenesis resulted in decreased litter size and increased incidence of external fetal malformations. This was thought to be related to decreased function of an inverted yolk sac, the primary nutritive organ for rat pups in utero (14). Holson et al. (15) performed a similar study on dogs which did not reveal a statistically significant difference in fetal malformations or other study end-points when compared to control. Canines and humans do not have an inverted yolk sac. Thus, it has been hypothesized that teratogenic effects of HBOC-201 do not apply to humans, however, more studies are needed. At least one US expanded access study allows pregnant women with the potential of massive blood loss (e.g. those with placenta accreta, placenta percreta) to consent to the study while still pregnant. However, HBOC-201 cannot be given until after delivery.
HBOC-201 in this case was utilized as a means to reverse severe end-organ damage due to anemia. This Jehovah’s Witness patient refused blood products, citing religious beliefs. Jehovah’s Witnesses in general will not receive “primary” blood components which include red blood cells, platelets and plasma. Other components, including albumin, clotting factors and HBOCs are considered “conscience items” through the church, where-in the individual can decide for themselves if they wish to receive them (5). With an estimated 1.2 million Jehovah’s Witnesses in the United States alone, alternative treatment options for this patient population are imperative (5).
While transfusion of allogeneic blood products remains the standard of care for treatment of severe post-partum hemorrhage, there are certain situations where this is not available. These might include lack of resources in a rural setting, blood product shortages, and inability to cross-match blood products given patient antibodies or patient denial of blood products due to personal or religious beliefs. HBOC’s are currently not approved for use in the United States, however they can be used on a limited compassionate use basis with FDA IND and local IRB approval, either as part of a planned expanded use study or on an emergency approval basis. Referral to a center with an expanded use protocol should be considered for a woman with the potential for massive bleeding who cannot receive RBC.
References
- Enakpene CA, Morhason-Bello IO, Enakpene EO, Arowojolu AO, Omigbodun AO. Oral misoprostol for the prevention of primary post-partum hemorrhage during third stage of labor. J Obstet Gynaecol Res. 2007 Dec;33(6):810-7. [CrossRef] [PubMed]
- Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014 2(6):e323–e333.[CrossRef] [PubMed]
- Creteur J, Vincent JL. Hemoglobin solutions. Crit Care Med. 2003 Dec;31(12 Suppl):S698-707. [CrossRef] [PubMed]
- Marinaro J, Smith J, Tawil I, Billstrand M, Crookston KP. HBOC-201 use in traumatic brain injury: case report and review of literature. Transfusion. 2009 Oct;49(10):2054-9. [CrossRef] [PubMed]
- Epperla N, Strouse C, VanSandt AM, Foy P. Difficult to swallow: warm autoimmune hemolytic anemia in a Jehovah's Witness treated with hemoglobin concentrate complicated by achalasia. Transfusion. 2016 Jul;56(7):1801-6. [CrossRef] [PubMed]
- Greenburg AG, Kim HW. Hemoglobin-based oxygen carriers. Crit Care. 2004;8 Suppl 2:S61-4. [CrossRef] [PubMed]
- Fitzgerald MC, Chan JY, Ross AW, Liew SM, Butt WW, Baguley D, et al. A synthetic haemoglobin-based oxygen carrier and the reversal of cardiac hypoxia secondary to severe anaemia following trauma. Med J Aust. 2011 May;194(9):471-3. [PubMed]
- Mongan PD, Moon-Massat PF, Rentko V, Mihok S, Dragovich A, Sharma P. Regional blood flow after serial normovolemic exchange transfusion with HBOC-201 (Hemopure®) in anesthetized swine. J Trauma. 2009 Jul;67(1):51-60. [CrossRef] [PubMed]
- Serruys PW, Vranckx P, Slagboom T, Regar E, Meliga E, de Winter RJ, et al. Haemodynamic effects, safety, and tolerability of haemoglobin-based oxygen carrier-201 in patients undergoing PCI for CAD. EuroIntervention. 2008 Mar;3(5):600-9. [CrossRef] [PubMed]
- Van Hemelrijck J, Levien LJ, Veeckman L, Pitman A, Zafirelis Z, Standl T. A safety and efficacy evaluation of hemoglobin-based oxygen carrier HBOC-201 in a randomized, multicenter red blood cell controlled trial in noncardiac surgery patients. Anesth Analg. 2014 Oct;119(4):766-76. [CrossRef] [PubMed]
- Jordan SD, Alexander E. Bovine hemoglobin: a nontraditional approach to the management of acute anemia in a Jehovah's Witness patient with autoimmune hemolytic anemia. J Pharm Pract. 2013 Jun;26(3):257-60. [CrossRef] [PubMed]
- Mer M, Hodgson E, Wallis L, Jacobson B, Levien L, Snyman J, et al. Hemoglobin glutamer-250 (bovine) in South Africa: consensus usage guidelines from clinician experts who have treated patients. Transfusion. 2016 Sep. [CrossRef] [PubMed]
- Donahue LL, Shapira I, Shander A, Kolitz J, Allen S, Greenburg G. Management of acute anemia in a Jehovah's Witness patient with acute lymphoblastic leukemia with polymerized bovine hemoglobin-based oxygen carrier: a case report and review of literature. Transfusion. 2010 Jul;50(7):1561-7. [CrossRef] [PubMed]
- Stump DG, Holson JF, Harris C, Pearce LB, Watson RE, DeSesso JM. Developmental toxicity in rats of a hemoglobin-based oxygen carrier results from impeded function of the inverted visceral yolk sac. Reprod Toxicol. 2015 Apr;52:108-17. [CrossRef] [PubMed]
- Holson JF, Stump DG, Pearce LB, Watson RE, DeSesso JM. Absence of developmental toxicity in a canine model after infusion of a hemoglobin-based oxygen carrier: Implications for risk assessment. Reprod Toxicol. 2015 Apr;52:101-7. [CrossRef] [PubMed]
Cite as: Mytinger A, Sheehan E, Blue N, Crookston KP, Saeed AI. Management of life threatening post-partum hemorrhage with HBOC-201 in a Jehovah’s witness. Southwest J Pulm Crit Care. 2017;14(4):177-84. doi: https://doi.org/10.13175/swjpcc031-17 PDF
March 2017 Critical Care Case of the Month
Kyle J. Henry, MD
Banner University Medical Center Phoenix
Phoenix, AZ USA
History of Present Illness
A 50-year-old man presented to the emergency room via private vehicle complaining of 5 days of intermittent chest and right upper quadrant pain. Associated with the pain he had nausea, cough, shortness of breath, lower extremity edema, and palpitations.
Past Medical History, Social History, and Family History
He had a history of hypertension and diabetes mellitus but was on no medications and had not seen a provider in years. He was disabled from his job as a construction worker. He had smoked a pack per day for 30 years. He was a heavy daily ethanol consumer. He had an extensive family history of diabetes.
Physical Examination
- Vitals: T 36.4 C, pulse 106/min and regular, blood pressure 96/69 mm Hg, respiratory rate 19 breaths/min, SpO2 98% on room air
- Lungs: clear
- Heart: regular rhythm without murmur.
- Abdomen: mild RUQ tenderness
- Extremities: No edema noted.
Electrocardiogram
His electrocardiogram is show in Figure 1.
Figure 1. Admission electrocardiogram.
Which of the following are true regarding the electrocardiogram? (Click on the correct answer to proceed to the second of seven pages)
- The lack of Q waves in V2 and V3 excludes an anteroseptal myocardial infarction
- The S1Q3T3 patter is diagnostic of a pulmonary embolism
- There are nonspecific ST and T wave changes
- 1 and 3
- All of the above
Cite as: Henry KJ. March 2017 critical care case of the month. Southwest J Pulm Crit Care. 2017;14(3):94-102. doi: https://doi.org/10.13175/swjpcc021-17 PDF
February 2017 Critical Care Case of the Month
Morgan Wong, DO
Nicholas Villalobos, MD
Department of Internal Medicine
University of New Mexico
Albuquerque, NM USA
History of Present Illness
A 68-year-old man presented to the emergency department with a one-day history of lower back pain, arthralgias, and malaise. The patient had a previous splenectomy and was concerned about influenza.
Past Medical History, Social History, and Family History
He has a history of osteoarthritis, seasonal allergies, and splenectomy. He is a nonsmoker. Family history is noncontributory.
Physical Examination
Upon admission, the patient’s vital signs were notable for a temperature of 35.3 degrees Celsius, blood pressure of 74/44 mmHg, oxygen saturation of 85% on room air with a respiratory rate of 24 breaths per minute. Physical exam was prominent for non-pitting edema of the distal upper and lower extremities, as well as diffuse macular rash of the palms and soles.
Laboratory
CBC
- White blood cell count of 6.77 X103 cells/uL
- Hemoglobin of 13.8 gm/dL
- Hematocrit of 43.7%
- Platelet count of 19 x 103 /uL
Chemistry
- Creatinine of 3.0 mg/dL
- CO2 < 10 mmol/L
- Anion gap >18 mmol/L
- Liver function tests
- Alanine aminotransferase (ALT) of 511 U/L
- Aspartate aminotransferase (AST) of 529 U/L
- Total bilirubin of 1.0 mg/dL
Coagulation
- INR of 2.07
- Prothromin time of 22.5 seconds
- Partial thromoboplastin time of 82.3 seconds
- Fibrinogen level was 71 mg/dL
Arterial blood gases
- pH of 6.91
- pCO2 54 mmHg
- pO2 263
- HCO3 of 7.7 mmol/L
Procalcitonin >200 ng/ml.
His blood peripheral smear was examined.
Figure 1: Peripheral blood smear on admission.
Given the results of the preliminary laboratory results and peripheral smear what hematologic abnormality are you most concerned with at this time? (Click on the correct answer to proceed to the second of five pages)
- Autoimmune hemolytic anemia (AIHA)
- Disseminated intravascular coagulopathy (DIC)
- Microangiopathic hemolytic anemia (MAHA)
- Thrombotic thrombocytopenic purpura (TTP)
Cite as: Wong M, Villalobos N. February 2017 critical care case of the month. Southwest J Pulm Crit Care. 2017;14(2):54-9. doi: https://doi.org/10.13175/swjpcc144-16 PDF
August 2016 Critical Care Case of the Month
Jillian L. Deangelis, APRN, CNP
Theodore Loftsgard APRN, ACNP
Department of Anesthesiology
Mayo Clinic Minnesota
Rochester, MN 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): Jillian L. Deangelis, MS, APRN, CNP. 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 this activity I will be better able to:
- Correctly interpret and identify clinical practices supported by the highest quality available evidence.
- Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
- Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
- Will integrate new treatment options in discussing available treatment alternatives 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, 2015-December 31, 2016
Financial Support Received: None
History of Present Illness
The patient is a previously healthy, albeit anxious, 15-year-old girl seen by her primary care physician. She has had several months of general malaise and ongoing fatigue and an increased frequency in night terrors over the past few weeks. Her family attributes this to stress of school and her new job. She was noted to have lost 3 kg in the previous nine weeks.
PMH, SH, and FH
Her PMH was unremarkable. She is a student and denies smoking, drinking or drug abuse. Her family history is noncontributory.
Physical Examination
- Vital signs: BP 100/60 mm Hg, P 90 beats/min and regular, R 16 breaths/min, T 100.8 ºF, BMI 15.
- Diffuse, non-tender lymphadenopathy through the submandibular and upper anterior cervical chains.
- Lungs: clear
- Heart: regular rhythm without murmur.
- Abdomen: slightly rounded and firm.
Which of the following are diagnostic considerations at this time? (Click on the correct answer to proceed to the second of seven panels)
Cite as: Deangelis JL, Loftsgard T. August 2016 critical care case of the month. Southwest J Pulm Crit Care. 2016;13(2):46-53. doi: http://dx.doi.org/10.13175/swjpcc056-16 PDF
July 2016 Critical Care Case of the Month
Warren Carll, DO
Susanna Tan, MD
Shannon Skinner, MD
Maricopa Integrated Health System
Phoenix, AZ 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): Warren Carll, DO. 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 this activity I will be better able to:
- Correctly interpret and identify clinical practices supported by the highest quality available evidence.
- Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
- Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
- Will integrate new treatment options in discussing available treatment alternatives 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, 2015-December 31, 2016
Financial Support Received: None
History of Present Illness
The patient is a 20-year-old man with admitted to Maricopa Integrated Health System unconscious after being found down on a hiking trail.
Past Medical History
Hypertension and morbid obesity.
Physical Examination
- Vital signs: BP 90/60 mm Hg, P 128 beats/min, Respiration 28 breaths/min, T 105.8º F, SpO2 98% on 2 L/min by NC.
- General: he is unresponsive to verbal stimuli but withdraws from pain
- Neck: there is no jugular venous distention. Thyroid is not palpable.
- Lungs: clear
- Heart: Regular tachycardia without murmur
- Abdomen: Obese but soft without organomegaly or tendernesses
- Extremities: apparent burns over both lower extremities
Which of the following should be done initially? (Click on the correct answer to proceed to the second of five panels)
- Cool the patient as quickly as possible
- Cool the patient slowly to prevent cerebral edema
- Aggressively administer normal saline to correct hypotension
- 1 and 3
- All of the above
Cite as: Carll W, Tan S, Skinner S. July 2016 critical care case of the month. Southwest J Pulm Crit Care. 2016;13(1):9-14. doi: http://dx.doi.org/10.13175/swjpcc046-16 PDF
Ultrasound for Critical Care Physicians: Now My Heart Is Still Somewhat Full
Krystal Chan, MD
Bilal Jalil, MD
Department of Internal Medicine
University of New Mexico School of Medicine
Albuquerque, NM USA
A 48-year-old man with a history of hypertension, intravenous drug abuse, hepatitis C, and cirrhosis presented with 1 day of melena and hematemesis. While in the Emergency Department, the patient was witnessed to have approximately 700 mL of hematemesis with tachycardia and hypotension. The patient was admitted to the Medical Intensive Care Unit for hypotension secondary to acute blood loss. He was found to have a decreased hemoglobin, elevated international normalized ratio (INR), and sinus tachycardia. A bedside echocardiogram was performed.
Figure 1. Apical four chamber view of the heart.
Figure 2. Longitudinal view of the inferior vena cava entering into the right atrium.
What is the best explanation for the echocardiographic findings shown above? (Click on the correct answer for an explanation and discussion)
Cite as: Chan K, Jalil B. Ultrasound for critical care physicians: now my heart is still somewhat full. Southwest J Pulm Crit Care. 2016;12(6):236-9. doi: http://dx.doi.org/10.13175/swjpcc054-16 PDF
May 2016 Critical Care Case of the Month
Layth Al-Jashaami, MD
Yousef Usta, MD
Negin N. Blattman, MD
Rakesh Nanda, MD
Phoenix VA Health Care System
650 E Indian School Road
Phoenix, Arizona, 85012 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): Layth Al-Jashaami, 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 this activity I will be better able to:
- Correctly interpret and identify clinical practices supported by the highest quality available evidence.
- Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
- Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
- Will integrate new treatment options in discussing available treatment alternatives 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, 2015-December 31, 2016
Financial Support Received: None
History of Present Illness
A 50-year-old African American woman presented with weakness, altered mental status and constipation of 12 days duration. She was complaining of abdominal distension with diffuse pain and bloating. She denied melena, hematochezia or hematemesis. She had a history weight loss, anorexia and fatigue which had evolved over the past few months leading to recent severe weakness and inability to get out of bed.
Past Medical History, Social History and Family History
Her past medical history included HIV infection with AIDS and noncompliance with her antiretroviral medications. Her most recent CD4 count was <20 cells/uL and viral load of 554,483 copies/mL.
Physical Examination
Vital signs: Blood pressure, 120/80 mmHg, heart rate, 105/min, temperature, 98.6° and respiratory rate, 20/min.
General: Physical examination showed a lethargic female who was poorly responsive to questioning.
Abdomen: Distended, tympanic abdomen with hypoactive bowel sounds and diffuse tenderness.
Radiography
Plain x-ray examination of the abdomen on admission is shown in Figure 1.
Figure 1. Admission x-ray of the abdomen.
Which of the following are possible causes of the patient's complaints, physical findings and abdominal x-ray findings? (Click on the correct answer to proceed to the second of six panels)
Cite as: Al-Jashaami L, Usta Y, Blattman NN, Nanda R. May 2016 critical care case of the month. Southwest J Pulm Crit Care. 2016 May;12(5):171-9. doi: http://dx.doi.org/10.13175/swjpcc038-16 PDF
April 2016 Critical Care Case of the Month
Samir Sultan, DO
Banner University Medical Center Phoenix
Phoenix, AZ
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): Samir Sultan, DO. 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 this activity I will be better able to:
- Correctly interpret and identify clinical practices supported by the highest quality available evidence.
- Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
- Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
- Will integrate new treatment options in discussing available treatment alternatives 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, 2015-December 31, 2016
Financial Support Received: None
History of Present Illness
The patient is a 22-year-old African-American man who was initially seen following a rapid response team called to the neonatal intensive care unit for a seizure. He was visiting his newborn child. The nurses described the seizure as tonic-clonic which resolved spontaneously without treatment before the rapid response team arrived.
Past Medical History, Family History and Social History
The patient has a past medical history of a brain aneurysm treated by coil embolization 2 years earlier. He had no complications of the embolization including seizures. Family history is unremarkable. He smokes 1-2 cigars per day but does not drink alcohol.
Physical Examination
He was drowsy when initially seen but the drowsiness resolved in about 5 minutes. The physical examination was unremarkable and there were no focal neurologic signs.
What should be next? (Click on the correct answer to proceed to the second of seven panels)
- CT scan of the head
- Phenytoin administration
- Metabolic screening (BUN, glucose and electrolytes)
- 1 and 3
- All of the above
Cite as: Sultan S. April 2016 critical care case of the month. Southwest J Pulm Crit Care. 2016 Apr;12(4): . doi: http://dx.doi.org/10.13175/swjpcc033-16 PDF
March 2016 Critical Care Case of the Month
Theo Loftsgard APRN, ACNP
Joel Hammill APRN, CNP
Mayo Clinic Minnesota
Rochester, MN 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): Theo Loftsgard APRN, ACNP. 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 this activity I will be better able to:
- Correctly interpret and identify clinical practices supported by the highest quality available evidence.
- Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
- Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
- Will integrate new treatment options in discussing available treatment alternatives 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, 2015-December 31, 2016
Financial Support Received: None
History of Present Illness
A 58-year-old man was admitted to the ICU in stable condition after an aortic valve replacement with a mechanical valve.
Past Medical History
He had with past medical history significant for endocarditis, severe aortic regurgitation related to aortic valve perforation, mild to moderate mitral valve regurgitation, atrial fibrillation, depression, hypertension, hyperlipidemia, obesity, and previous cervical spine surgery. As part of his preop workup, he had a cardiac catheterization performed which showed no significant coronary artery disease. Pulmonary function tests showed an FEV1 of 55% predicted and a FEV1/FVC ratio of 65% consistent with moderate obstruction.
Medications
Amiodarone 400 mg bid, digoxin 250 mcg, furosemide 20 mg IV bid, metoprolol 12.5 mg bid. Heparin nomogram since arrival in the ICU.
Physical Examination
He was extubated shortly after arrival in the ICU. Vitals signs were stable. His weight had increased 3 Kg compared to admission. He was awake and alert. Cardiac rhythm was irregular. Lungs had decreased breath sounds. Abdomen was unremarkable.
Laboratory
His admission laboratory is unremarkable and include a creatinine of 1.0 mg/dL, blood urea nitrogen (BUN) of 18 mg/dL, white blood count (WBC) of 7.3 X 109 cells/L, and electrolytes with normal limits.
Radiography
His portable chest x-ray is shown in Figure 1.
Figure 1. Portable chest x-ray taken on admission to the ICU.
What should be done next? (Click on the correct answer to proceed to the second of five panels)
- Bedside echocardiogram
- Diuresis with a furosemide drip because of his weight gain and cardiomegaly
- Observation
- 1 and 3
- All of the above
Cite as: Loftsgard T, Hammill J. March 2016 critical care case of the month. Southwest J Pulm Crit Care. 2016;12(3):81-8. doi: http://dx.doi.org/10.13175/swjpcc018-16 PDF
February 2016 Critical Care Case of the Month
Thomas M. Stewart, MD
Bhargavi Gali, MD
Department of Anesthesiology
Mayo Clinic Minnesota
Rochester, MN USA
Case Presentation
A 32 year-old, previously healthy, female hospital visitor had been participating in a family care conference regarding her critically ill grandmother admitted to the cardiac intensive care unit. During the care conference, she felt unwell and had some mild chest discomfort; she collapsed and cardiopulmonary resuscitation (CPR) was initiated (1). Upon arrival of the code team, she was attached to the monitor and mask ventilation was initiated. Her initial rhythm is shown in Figure 1.
Figure 1. Initial rhythm strip.
In addition to DC cardioversion which of the following should be administered immediately? (Click on the correct answer to proceed to the second of four panels)
Cite as: Stewart TM, Gali B. February 2016 critical care case of the month. Southwest J Pulm Crit Care. 2016;12(2):41-5. doi: http://dx.doi.org/10.13175/swjpcc011-16 PDF
December 2015 Critical Care Case of the Month
Samir Sultan, DO
Banner University Medical Center Phoenix
Phoenix, AZ
History of Present Illness
The patient is a 32-year-old woman who presented with flank pain for 3 days to an outside hospital. She was diagnosed with pyelonephritis and begun on ceftriaxone. She was discharged against medical advice on cephalexin.
She returned to the same hospital 3 days later by ambulance with labored breathing and weakness and was emergently intubated. She was transferred for ventilator management and respiratory failure.
Past Medical History
She has a long history of poorly controlled diabetes mellitus.
Physical Examination
She is orally intubated and sedated.
Vitals: Temperature - 100.9º F, Blood Pressure - 117/75 mm Hg, Heart Rate - 148 beats per minute, Respiratory Rate - 31 breaths/min, SpO2 - 88 % on assist control of 30, tidal volume of 350 mL, PEEP 15, and an FiO2 100%.
There is scatted rhonchi and rales but the remainder of the physical examination is unremarkable.
Radiography
Her admission portable chest X-ray is shown in Figure 1.
Figure 1. Admission portable AP of the chest.
Which of the following should be ordered as part of her initial work-up? (Click on the correct answer to proceed to the second of five panels).
- Administer broad spectrum antibiotics
- Blood and urine cultures
- Rapid influenza test
- 1 and 3
- All of the above
Cite as: Sultan S. December critical care case of the month. Southwest J Pulm Crit Care. 2015;11(6):246-51. doi: http://dx.doi.org/10.13175/swjpcc147-15 PDF
November 2015 Critical Care Case of the Month
Samir Sultan, DO
Banner University Medical Center Phoenix
Phoenix, AZ
History of Present Illness
A 39-year-old Caucasian woman was admitted to the ICU with worsening dyspnea and increasing oxygen requirements. Her lips turned blue with minimal activity. She was admitted to another hospital 5 months earlier with pneumonia. At discharge she was placed on oxygen. At follow-up with her pulmonologist, she was diagnosed with sleep apnea.
Past Medical History, Family History, Social History
- She has a history of an optic glioma at age 7 with resection followed by radiation therapy and development of panhypopituitarism.
- Liver cirrhosis diagnosed in 2014 with presentation of hematemesis.
- Type 2 diabetes mellitus
- Denies tobacco, ethanol, or illicit drug use.
- There is a family history of diabetes and liver cirrhosis
Physical Examination
- Vital signs:110 / 86, HR 97, RR 16, 88% on 6 liter O2
- General: obese female (BMI 35) in no apparent distress
- Chest: Clear to auscultation bilaterally
- Cardiovascular: regular rate without murmur or rub
- The remainder of the physical exam is normal
Radiography
A chest x-ray was interpreted as normal.
Laboratory
- CBC: hemoglobin 13.8 gm/dL, WBC 7 X 103 cells/microliter with a normal differential
- Basic metabolic panel: Na+ 132 mEq/L, K+ 4 mEq/L, Cl- 100 mEq/L, HCO3- 22 mEq/L, glucose 150 mg/dL.
- Arterial blood gases (ABGs): PaO2 35 mm Hg, PaCO2 37 mm Hg, pH 7.43
Which of the following is/are not possible cause(s) of hypoxemia in this patient? (Click on the correct answer to proceed to the second of six panels)
- Decreased diffusion (alveolar capillary block)
- Ventilation-perfusion mismatch
- Hypoventilation
- 1 and 3
- All of the above
Cite as: Sultan S. November 2015 critical care case of the month. Southwest J Pulm Crit Care. 2015;11(5):209-15. doi: http://dx.doi.org/10.13175/swjpcc137-15 PDF
August 2015 Critical Care Case of the Month: A Diagnostic Branch of Medicine
William T. Love, MD
Karen L. Swanson, DO
Department of Pulmonary Medicine
Mayo Clinic Arizona
Scottsdale, AZ
History of Present Illness
A 66-year-old man had undergone an orthotopic heart transplantation on March 28th, 2015 due to end-stage cardiomyopathy. During a recent hospitalization from 6/26-7/2 a transbronchial lung biopsy was suggestive of subacute rejection. He was treated with:
- Plasmapheresis x 3
- Intravenous immunoglobulin (IVIG)
- 500 mg Solu-Medrol daily
- Tacrolimus held as supra-therapeutic level of 16.2
- Mycophenolate decreased to 500mg BID
- Prednisone at 10mg BID on discharge
On July 3rd he began having cough productive of clear sputum, nausea, vomiting, and headache. Subsequently he had body aches, subjective fever, chills, night sweats, and a poor appetite with a 4 kg weight loss over the last week. There was also a history of several falls after “losing his balance".
Past Medical History
There was also a history of type 2 diabetes mellitus, chronic kidney disease, coronary artery disease with coronary artery bypass grafting in 2000.
Physical Examination
- Vital signs: T-37.1, HR-100, BP-130/88, RR-22, 96% RA
- Heart: regular rate & rhythm. 2/6 Systolic Murmur
- Lungs: clear to auscultation bilaterally
Laboratory
- Hemoglobin 9.7, WBC 6.3, creatinine 2.2, mildly elevated AST/ALT
- Lumbar Puncture– Protein 58 mg/dL, Glucose 46 mg/dL, 47 Nucleated cells
Radiography
A chest x-ray was performed (Figure 1).
Figure 1. Admission PA of the chest.
Based on the chest x-ray and lumbar puncture, which of the following are true? (Click on the correct answer to proceed to the second of four panels)
- The chest x-ray and lumbar puncture findings in this clinical situation suggest cancer metastatic to the lung and brain
- The chest x-ray and lumbar puncture findings in this clinical setting suggest an infection involving the lung and brain
- The clinical findings suggest granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis)
- The clinical findings are suggestive of acute rejection
- The clinical findings are suggestive of tuberculosis
Reference as: Love WT, Swanson KL. August 2015 critical care case of the month: a diagnostic branch of medicine. Southwest J Pulm Crit Care. 2015;11(2):59-65. doi: http://dx.doi.org/10.13175/swjpcc100-15 PDF
June 2015 Critical Care Case of the Month: Just Ask the Nurse
Robert A. Raschke, MD
Banner University Medical Center
Phoenix, AZ
History of Present Illness
A 61-year-old police officer had just finished delivering a speech at a law enforcement conference in Phoenix when he briefly complained of chest pain or chest tingling before lapsing into a mute state. He became diaphoretic cyanotic, and vomited. Emergency medical services was called. They noted a blood pressure of 80/50 mm Hg, a pulse of 45, temperature of 95º F, a respiratory rate of 12, and widely dilated pupils. He was transported to the emergency room.
PMH, SH, FH, Medications
Unknown.
Physical Examination
Vital signs: blood pressure 120/75 mm Hg by oscillometric thigh cuff, pulse 43 and irregular, temperature 96º F, respiratory rate 10, SpO2 96% on O2 @ 5L/min by nasal cannula
Neck: No JVD.
Lungs: Poor inspiratory effort
Heart: Irregular rhythm without a murmur
Neurological:
- Delirious – mute – won’t obey commands or track with his eyes
- Pupils 3 mm reactive
- Withdrew 3 extremities to nail bed pressure – he will defend his left arm with his right arm
He suddenly became asystolic and cardiopulmonary resuscitation was begun. After about a minute a femoral pulse could be felt.
Which of the following are indicated at this time? (Click on the correct answer to proceed to the second of five panels)
Reference as: Raschke RA. June 2015 critical care case of the month: just ask the nurse. Southwest J Pulm Crit Care. 2015;10(6):323-9. doi: http://dx.doi.org/10.13175/swjpcc077-15 PDF
Acute Pregabalin Withdrawal: A Case Report and Review of the Literature
Jaclyn A. Barrett, PharmD
Lindsay M. Kittler, PharmD, BCPS
Clement Singarajah, MD, FCCP
Phoenix VA Medical Center
Phoenix, AZ 85012
Abstract
Objective: Pregabalin is a commonly prescribed GABA analog most commonly used for the treatment of neuralgia. Recently, case reports on pregabalin have been published describing episodes that may be associated with withdrawal-like symptoms after extended or aggressive therapy. This report describes a case in which long term exposure of high dose pregabalin may have resulted in acute withdrawal, and outlines the subsequent medical management of these symptoms.
Case Summary: A 61-year-old male presenting with severe agitation presumed to be withdrawal from long term and high dose exposure to pregabalin. Medical management included the use of haloperidol, diphenhydramine, lorazepam and the addition of clonidine over the course of several days for the pharmacological management of withdrawal symptoms.
Discussion: Although case reports are available to guide clinicians in the recognition of acute pregabalin withdrawal, definitive evidence on how best to treat these patients remains severely limited. With an increase in the prescribing practices of pregabalin, insight into the acute management by fellow clinicians is further needed.
Conclusion: Caution must be practiced when prescribing and educating patients on the use of pregabalin to prevent associated withdrawal-like symptoms. In addition, documentation by the medical community on methods utilized to treat pregabalin withdrawal syndromes remains crucial for the advancement of patient care. Benzodiazepines and clonidine are the current therapies that have been documented as potentially effective treatment modalities at this time.
Introduction
Pregabalin is a gamma-aminobutyric acid (GABA) analogue currently FDA labeled for diabetic peripheral neuropathy, fibromyalgia, neuropathic pain, partial seizures and postherpetic neuralgia, and is used off-label in various psychiatric disorders. It is proposed that pregabalin binds strongly to an alpha-2-delta subunit on voltage gated calcium channels within the central nervous system. Pro-nociceptive neurotransmitter release that is dependent upon calcium is thereby reduced. Additional mechanisms for pregabalin’s efficacy may be comprised of noradrenergic and serotonergic pathways involved in pain transmission (1).
Case Presentation
We report the case of a 61-year-old man who presented with sudden and severe withdrawal like symptoms characterized by family as extreme agitation with combative behavior, diaphoresis, tachycardia, hypertension, tremors, and incontinent diarrhea. Reportedly, prior to admission, the patient had become increasingly somnolent with multiple falls and psychotic behavior similar to one responding to internal stimuli. A review of his home prescription vials revealed a presumed, excessive consumption of immediate-release oxycodone and pregabalin over the last few days and up to a week. His past medical history included chronic obstructive pulmonary disease, osteoarthritis, neuropathic pain, hypothyroidism, hyperlipidemia, anxiety and major depressive disorder. A thyroid stimulating hormone level was checked upon admission and was within normal limits with no other metabolic explanation for his symptoms identified. The patient did present with a prior medical history of opioid abuse with previous enrollments in substance abuse programs, but compliance with his current pain management contract was confirmed using the state’s controlled substance prescription monitoring program database.
Upon admission through the emergency room, the patient remained severely agitated with increasingly combative behavior despite the administration of the antipsychotic, haloperidol. Without relief, the benzodiazepine, lorazepam, was administered resulting in a paradoxical effect causing increased aggression and agitation and thus discontinued. Implementation of scheduled hydromorphone was administered for acute opioid withdrawal but similarly provided minimal symptom abatement yet, maintained adequate analgesia. After medication review and reconciliation, the patient was currently on a prescribed, scheduled dose of pregabalin 300 mg twice daily over the course of approximately eight months for the treatment of neuropathic pain. Although initially concerned for potential overdose, all symptoms upon presentation were deemed to be consistent with a withdrawal syndrome, pregabalin being the most likely culprit given lack of symptom abatement with the use of benzodiazepines and opioids with no other likely cause upon review of his home medications and laboratory data.
After transferring to the Intensive Care Unit, the patient was further treated with intravenous haloperidol 10 mg and diphenhydramine 50 mg every 4 hours providing only minimal relief while protecting both the safety of the patient and staff. Management of acute pregabalin withdrawal was further complicated by the inability to provide pregabalin orally, due to disorientation and the physical inability to maintain placement of a nasogastric tube. Sedation and mechanical ventilation was not an option as the patient’s established wishes were a Do Not Intubate (DNI) status. Sublingual clonidine 0.1 mg was later administered every four hours and up to every hour if needed, in addition to the haloperidol and diphenhydramine. The anti-adrenergic agent clonidine was most effective in providing withdrawal symptom reduction, and the haloperidol and diphenhydramine were rapidly tapered off. In addition, our patient developed urinary retention necessitating the discontinuation of diphenhydramine. The discontinuation of diphenhydramine lead to a retrial of lorazepam which provided effective relief for the management of his later course agitation with no paradoxical agitation observed.
This case demonstrates an issue of common occurrence, where a patient is withdrawing clinically from a drug with often non-specific symptom manifestations. Further confounding this clinical presentation, several possible sources of drug withdrawal required the medical team to address each drug individually in order to identify the offending agent. With this in mind, withdrawal from pregabalin, although not often considered a drug of abuse or associated with intense withdrawal, may only be identified by ruling out other suspected agents, such as in this patient scenario.
Discussion
In review of current literature, case reports have arisen that describe symptoms of withdrawal from abrupt discontinuation of pregabalin. Several case reports describe a withdrawal-like syndrome to include signs and symptoms such as agitation, anxiety, confusion, gastrointestinal distress, tachycardia and palpitations, similar to benzodiazepine withdrawal (2-4).
Oaklander and Buchbinder (2) report a case involving an 80-year-old woman prescribed pregabalin 125 mg three times daily for 49 weeks as treatment for postherpetic neuralgia. Within 36 hours of abrupt discontinuation, the patient developed severe nausea, headache, imbalance, delirium and anorexia. Over the course of several weeks, the patient developed hemodynamic instability and continued to experience episodes of ataxia for a six month duration.
Another report by Karosin et al. (3), describes a 47-year-old male who reportedly consumed a total daily dose of 7,500 mg of pregabalin daily in addition to alcohol and cocaine abuse. In a failed attempt to wean off pregabalin the patient developed what was described to be vegetative withdrawal symptoms, sweating, restlessness, hypertension, tremor and pregabalin cravings. Upon admission, the patient received treatment with benzodiazepines without relief and a slow taper of pregabalin was initiated yet, cravings continued which ultimately resulted in the patients continued abuse of this GABA analog.
In a case report by Norgaard et al. (4), a 38 year-old man was self-administering 8.4 g pregabalin daily and within 36 hours of cessation of pregabalin developed auditory hallucinations and suicidal ideation in addition to sweating, anxiety and tachycardia. Pregabalin was reinitiated at 600 mg per day in addition to supplemental chlordiazepoxide and quetiapine. Acute symptoms resolved within 48 hours yet the symptoms of psychosis remained present until several weeks after discontinuation.
In addition, case reports regarding gabapentin withdrawal have been published to include similar clinical presentations. Gabapentin, another GABA analog, is FDA approved for the treatment epilepsy, neuralgia and restless leg syndrome, and is widely used in the prophylaxis of migraines, headaches and ethanol withdrawal (5). It is hypothesized that the mechanism of withdrawal is associated with increased activity of the enzyme responsible for producing GABA, similar to the mechanism behind ethanol and benzodiazepine withdrawal (6).
Hellwig et al. (6) and Mah et al. (7), describe similar symptoms of irritability, confusion and agitation unrelieved by the administration of benzodiazepines. Gabapentin was identified as the causative agent of withdrawal after reinstatement of the GABA analog provided relief in both case reports. In addition to drug related factors, potential patient related risk factors that may increase the susceptibility of withdrawal include advanced age and history of psychiatric illness.
Currently, pregabalin is a schedule V controlled substance due to its potential for addiction and abuse (8). According to the manufacturer, there are no current recommendations for the management of an acute drug withdrawal syndrome from pregabalin, yet current practice suggests that a gradual taper, generally recommended with all extended controlled substance therapy, may be warranted. This report suggests that clonidine may be an effective agent in the management of acute agitation associated with pregabalin withdrawal. Literature has historically supported the use of clonidine in a variety of drug withdrawal syndromes owing to its known central alpha 2 agonist activity, but remains underutilized amongst providers in current practice (9-11). Another alternative to consider is dexmedetomidine, a centrally acting, alpha 2 adrenoceptor agonist which has demonstrated its efficacy as an adjunctive treatment for refractory alcohol withdrawal (12). Due to concomitant hypertension and institutional cost, dexmedetomidine was considered second line in the event that clonidine was ineffective for our patient.
Although case reports are available to guide clinicians in the recognition of acute pregabalin withdrawal, definitive evidence on how best to treat these patients remains severely limited. With an increase in the prescribing practices of pregabalin, insight into the acute management by fellow clinicians is further needed to provide evidence-based guidance in the management of these patients. As for our clinical case of acute pregabalin withdrawal in the presence of hallucinatory features, we advise against the use of benzodiazepines due to the risks of paradoxical agitation, and would suggest withholding their use until the latter stages of withdrawal. If possible, as was not in our case, initiating a pregabalin taper would ideally preferred. We also propose that the use of clonidine has clinically shown, as demonstrated in this patient case, to provide appropriate supportive treatment for the management of acute pregabalin withdrawal.
References
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Pregabalin. DrugPoint Summary. Micromedex. Truven Health Analytics, Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed April 26, 2014.
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Oaklander AL, Buchbinder BR. Pregabalin-withdrawal encephalopathy and splenial edema: a link to high-altitude sickness? Ann Neurol. 2005;58(2):309-12. [CrossRef] [PubMed]
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Karosin C, Kofler M, Mayr A, et al: Pregabalin: A treatment option for dystonia? Neurol Sci. 2012;33(2):351-4. [CrossRef] [PubMed]
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Nordgaard J, Jurgens G. A case of pregabalin abuse. Clin Toxicol. 2013;51(4):320
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Gold Standard, Inc. Gabapentin. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology-ip.com/Forms/drugoptions.aspx?cpnum=271&n=Gabapentin&t=0 Accessed: 5/19/2015.
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Hellwig TR, Hammerquist R, Termaat J. Withdrawal symptoms after gabapentin discontinuation. Am J Health Syst Pharm. 2010;67:910-2. [CrossRef] [PubMed]
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Mah L, Hart M. Gabapentin withdrawal: case report in an older adult and review of the literature. J Am Geriatr Soc. 2013;61(9):1635-7. [CrossRef] [PubMed]
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LYRICA® (pregabalin) CV Safety Info. Available at: http://www.lyrica.com. Accessed April 27, 2014.
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Baumgartner GR, Rowen RC. Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome. Arch Intern Med. 1987;147:1223-6. [CrossRef] [PubMed]
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Baumgartner GR, Rown RC. Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a randomized, controlled clinical trial. South Med J. 1991;84:312-21. [CrossRef] [PubMed]
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Robinson BJ, Robinson GM, Mailing TJB, Johnson RH. Is clonidine useful in the treatment of alcohol withdrawal? Alcohol Clin Exp Res. 1989;13:95-8. [CrossRef] [PubMed]
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Tolonen J, Rossinen J, Alho H, Harjola VP. Dexmedetomidine in addition to benzodiazepine-based sedation in patients with alcohol withdrawal delirium. Eur J Emerg Med. 2013;20:425. [CrossRef] [PubMed]
Reference as: Barrett JA, Kittler LM, Singarajah C. Acute pregabalin withdrawal: a case report and review of the literature. Southwest J Pulm Crit Care. 2015;10(5):306-10. doi: http://dx.doi.org/10.13175/swjpcc059-15. PDF
May 2015 Critical Care Case of the Month: An Infected Leg
Sandra L. Till DO and Robert A. Raschke MD
Banner University Good Samaritan Medical Center
Phoenix, AZ
History of Present Illness
A 46-year-old transferred due to concern for necrotizing fasciitis. One the day prior to transfer purple discoloration was not noted in the lower portion of the left leg. On the day of transfer the leg became more purple, painful, and swollen. She presented to a pain clinic that advised her to go to an emergency room. The emergency room performed arterial Doppler ultrasound, which was normal and transferred her due to concern of necrotizing fasciitis.
Past Medical History, Social History and Family History
She has a past medical history of fibromyalgia. She had an extensive surgical history including an appendectomy, bladder implant, cholecystectomy, dilatation and curettage, esophageal repair, left femoral artery repair due to a motor vehicle accident, partial hysterectomy, left knee surgery, and several left leg operations with grafting. Family history was non-contributory. The patient was single with two children, and smoked 1-2 packs of cigarettes per day for 30 years. She denied any illicit drugs or alcohol abuse.
Medications
- Zolpidem
- Warfarin
- Furosemide
- Potassium Chloride
- Morphine sulfate
- Gabapentin
- Oxycodone
- Alprazolam
- Ondansetron
- Amitriptyline
Physical Examination
Vitals signs: Blood pressure 128/85 mm Hg, pulse 86 beat/min, respiratory rate 12, temperature 36.7º C, SPO2 96% on 2L/min of oxygen.
General: Non-toxic, alert and oriented x3, tearful due to pain.
The remainder of the physical examination was unremarkable except for the left lower extremity (Figure 1).
Figure 1. Photograph of the patient's left leg.
Which of the following are appropriate at this time? (Click on the correct answer to proceed to the second of five panels)
- Blood cultures
- Complete blood count, c-reactive protein, sodium, creatinine and glucose
- Surgery consult
- Wound culture
- All of the above
Reference as: Till SL, Raschke RA. May 2015 critical care case of the month: an infected leg. Southwest J Pulm Crit Care. 2015;10(5):208-15. doi: http://dx.doi.org/10.13175/swjpcc045-15 PDF
March 2015 Critical Care Case of the Month: It’s Not Always Sepsis
Dionne Morgan, MD
Carolyn H. Welsh, MD
University of Colorado and the Eastern Colorado Veterans Affairs Medical Center
Department of Medicine
Division of Pulmonary Sciences and Critical Care Medicine
Denver, CO
History of Present Illness
A 57-year-old man with multiple co-morbidities including diabetes mellitus presented with wet gangrene of the right foot and hypotension. He had diabetic ketoacidosis and acute kidney injury. He was admitted to the medical intensive care unit, given intravenous fluids and treated with insulin therapy, piperacillin/tazobactam and vancomycin. Initial blood cultures grew Methicillin-resistant Staphylococcus aureus (MRSA). The podiatry service performed a right transmetatarsal amputation. Subsequently, he did well and was transferred to a medical floor for further care.
Three weeks later, following resolution of the initial sepsis, he developed persistently high fevers with hemodynamic instability despite continued antibiotic therapy. He was transferred back to the MICU for presumed sepsis.
Past Medical History, Social History and Family History
The past medical history was significant for diabetes, hypertension, COPD, coronary artery disease and hepatitis C. He did not smoke nor drink alcohol. Family history was non-contributory.
Physical Examination
On readmission to the medical intensive care unit, the patient was noted to have a generalized maculopapular rash on both upper and lower extremities, torso, palms and soles of his feet, associated with facial and periorbital edema (Figure 1). There was no mucosal membrane involvement or lymphadenopathy. He was also febrile to 104o F, hypotensive to 80/50 mm Hg and icteric.
Figure 1. Image of rash.
Laboratory Studies
Initial labs showed elevated leukocyte count, BUN and creatinine with anion-gap metabolic acidosis but a normal liver enzyme profile. Repeat labs on readmission to the medical ICU were significant for severe leukocytosis, with marked eosinophilia, atypical lymphocytes on blood smear, acute transaminitis and hyperbilirubinemia.
Admission labs: White blood cell count (WBC) 29.9 x 1000 cells/μL. Eosinophils 0.0% (Normal 0.0 - 0.7%), AST 28 U/L, ALT 15 U/L, ALP 162 U/L, total bilirubin 0.2 mg/dL.
Labs on ICU readmission: White blood cell count (WBC) 35.7 x 1000 cells/ μL. Eosinophils 2.3% (Normal 0.0 -0.7%), AST 486 U/L, ALT 288 U/L, ALP 749 U/L, total bilirubin 4.3 mg/dL.
Which are components of the SIRS criteria? (click on the correct answer to proceed to the second of 4 panels)
Reference as: Morgan D, Welsh CH. March 2015 critical care case of the month: it's not always sepsis. Southwest J Pulm Crit Care. 2015;10(3):105-11. doi: http://dx.doi.org/10.13175/swjpcc029-15 PDF
Ultrasound for Critical Care Physicians: Now My Heart Is Even More Full
Bilal Jalil, MD
Michel Boivin, MD
Division of Pulmonary, Critical Care and Sleep Medicine
University of New Mexico School of Medicine
Albuquerque, NM
A 49-year-old man with type 2 diabetes, intravenous drug abuse and heart failure presented to the emergency room with 2 weeks of progressively worsening chest pain, lower extremity swelling and shortness of breath. The patient was found to have an elevated troponin as well as brain natriuretic peptide and the absence of ischemic electrocardiogram findings. The patient was admitted to the medical ICU for hypoxic respiratory failure and shock of uncertain etiology. Clinically he seemed to be in decompensated heart failure and a bedside echocardiogram was performed (Figures 1 and 2).
Figure 1. Parasternal short axis view at the level of the aortic valve
Figure 2. Apical 4 chamber view.
What is the best explanation for the echocardiographic findings shown above? (Click on the correct answer for the explanation)
Reference as: Jalil B, Boivin M. Ultrasound for critical care physicians: now my heart is even more full. Souhtwest J Pulm Crit Care. 2015;10(2):83-6. doi: http://dx.doi.org/10.13175/swjpcc020-15 PDF
February 2015 Critical Care Case of the Month: A Bloody Mess
Mily Sheth, MD
Carmen Luraschi, MD
Matthew P. Schreiber, MD, MHS
University of Nevada School of Medicine: Las Vegas
Department of Internal Medicine
Division of Pulmonary/Critical Care
Las Vegas, NV
History of Presenting Illness:
A 23-year-old Ethiopian woman with a known history of systemic lupus erythematosus (SLE) but of unknown duration presented with the chief complains of cough and generalised weakness for 1 week. She had a recent history of travelling to Ethiopia 3 months ago for 3 weeks. She complained of subjective fevers and one episode of blood tinged sputum. She also complained of fatigue and an episode of syncope which prompted her hospitalization.
PMH, SH and FH:
The patient has a past medical history of SLE diagnosed in Ethiopia of which no records were available. She is a student and denied alcohol, smoking or drug abuse. She denied any family history of autoimmune disorders. She did not take any medications at home.
Physical Examination:
Initial admission vital signs were temperature of 100.5 F, heart rate of 130, respiratory rate of 30 and blood pressure of 92/48. Oxygen saturation was 96% on 2 L/min via nasal cannula.
She appeared to be in moderate distress but was speaking in full sentences. Skin examination revealed a malar rash on her face. Her upper and lower extremities had excoriated plaques. Her anterior chest had flat non blanchable, macular rash. CVS examination revealed tachycardia without any murmurs. Respiratory exam was positive for bilaterally diffuse bronchial breath sounds. The remainder of her exam was within normal limits.
Laboratory and Radiology:
CBC: WBC 6.7 million cells/mcL, hemoglobin 7.1 g/dL, hematocrit 20.9, platelet 160,000 cells/mcL
Renal panel: within normal limits.
Troponin 0.01, creatine kinase 457 U/L, lactic acid 1.1 mm/L, HIV non-reactive
Liver function tests: AST 288 U/L, ALT 93 U/L alkaline phosphatase 136 IU/L, total bilirubin 0.9 mg/dL
Radiography:
Her initial chest x-ray is shown in figure 1. It was interpreted as showing diffuse pulmonary infiltrates, right lung greater than left. No pleural effusions. No pneumothorax.
Figure 1. Initial chest x-ray.
In a patient with these characteristics, which other test(s) would you order? (Click on the correct answer to proceed to the second of five panels)
- Arterial blood gases and lactic acid
- Cardiac angiogram
- Computed tomography (CT) of the chest without contrast
- VATS lung biopsy
- All of the above
Reference as: Sheth M, Luraschi C, Schreiber MP. February 2015 critical care case of the month: a blood mess. Southwest J Pulm Crit Care. 2015;10(2):63-9. doi: http://dx.doi.org/10.13175/swjpcc148-14 PDF
Analysis of a Fatal Left Ventricular Assist Device Infection: A Case Report and Discussion
Neal Stuart Gerstein, MD FASE1
Henry G. Chou, MD2
Andrew Lewis Dixon, MD1
1Department of Anesthesiology & Critical Care Medicine
University of New Mexico
Albuquerque, NM
2Department of Anesthesiology
Cedars-Sinai Medical Center
Los Angeles, CA
Introduction
Left ventricular assist device (VAD) therapy is an increasingly utilized treatment as a bridge to heart transplantation or as long-term destination therapy. Recent reports show there is a 22% - 32% incidence of VAD-associated infections with staphylococci and nosocomial gram-negative bacilli being the most common causative organisms (1,2). These organisms are often found in intensive care units, where they have the highest proportion of resistance, thus exposing already critically ill patients to the possibility of resistant organism VAD-associated infections (3). Mortality rates exceed 60% when sepsis develops in a patient with a continuous flow left VAD and infection is the number one cause of death in those awaiting cardiac transplantation (4,5). With continued left VAD use clinicians will likely see multidrug-resistant (MDR) or even pandrug-resistant organism VAD-associated infections. Clinicians need to be prepared to manage such an intimidating entity.
Case Report
We report a case of a 25 year-old male with a pandrug-resistant Pseudomonas aeruginosa VAD-associated infection. The patient’s medical history is significant for a diagnosis of idiopathic dilated cardiomyopathy refractory to maximal medical therapy requiring implantation of a HeartMate II (Thoratec Co., Pleasanton, CA, USA) continuous flow left VAD (Figure 1).
Figure 1. HeartMate II® left VAD schematic (reprinted with the permission of Thoratec Co., Pleasanton, CA, USA).
His course was complicated with multiple hospital admissions for recurrent VAD-associated infections and numerous episodes of P. aeruginosa bacteremia that had been treated with a multitude of antipseudomonal antibiotics. He presented to our hospital for management of severe volume overload in the setting of VAD-associated infections. Transesophageal echocardiography demonstrated a left ventricular ejection fraction of 24% with severe left and right ventricular dilatation. Chest x-ray revealed cardiomegaly and multiple devices including the left VAD (Figure 2).
Figure 2. Chest X-ray demonstrating an enlarged cardiac silhouette, the HeartMate II axial pump (*) with inflow (down arrow, ↓) and outflow (up arrow, ↑) cannulas, biventricular pacer with leads in right atrium (A), coronary sinus (B), and right ventricle (C) (dashed arrows).
Blood cultures revealed MDR P. aeruginosa; except for showing intermediate sensitivity to tobramycin there was resistance to all antimicrobials tested. In vitro synergy testing revealed modest bacterial inhibition when only colistin, fosfomycin, imipenem, and tobramycin were combined. After maximizing medical therapy, multiple left VAD pocket washings and implantation of tobramycin beads followed. Intraoperative findings included an encapsulated infection around the driveline and obvious infection of the left VAD pocket. Repeat blood cultures showed P. aeruginosa had developed resistance to all antimicrobials including tobramycin. Subsequently the left VAD was explanted and the patient was transitioned to an extracorporeal membrane oxygenator (ECMO) in attempt to clear the infection. He was then transitioned to a TandemHeart (CardiacAssist Inc., Pittsburgh, PA, USA), a percutaneous LVAD, as he was not dependent on ECMO for oxygenation. He was able to clear the bacteremia after removal of the infected HeartMate II while on colistin, fosfomycin, tobramycin, azithromycin and rifampin, but was not able to clear the remaining left VAD pocket infection, which again spread systemically. Despite maximal medical and surgical interventions, he died from profound septic shock and multisystem organ failure. To date this is the first known case of a pandrug-resistant P. aeruginosa VAD-associated infection reported in the literature.
Discussion
P. aeruginosa organisms have intrinsic resistance to numerous broad spectrum antibiotics, and can easily develop acquired resistance to most if not all available antimicrobial agents (3). Risk factors for the development of pandrug-resistant P. aeruginosa include previous treatment with antipseudomonal antibiotics and prolonged treatment times. Given our patient had multiple P. aeruginosa infections, treated with multiple rounds of antipseudomonal antibiotics, it is not surprising that pandrug-resistance developed. Few therapeutic options are available for treatment and no new agents are available to evade the known resistance mechanisms. Treatment can be optimized using synergistic combination therapy, which may be the only medical management option in patients with pandrug-resistant P. aeruginosa infections. Some have suggested that rifampin in combination with colistin may be a promising approach (3). Some experts recommend in vitro synergy testing when an organism is resistant to currently recommended antibiotic regimens (6,7). However, a recent review of antibiotic therapy for gram-negative infections describes the utility of in vitro synergy testing equivocal in the context of Pseudomonas infection (8). We managed our patient with combination therapy; however, not until pandrug-resistant P. aeruginosa was isolated did we introduce rifampin in combination with colistin.
A recent review of VAD-associated infections showed the majority were managed without surgical intervention; only 13% required surgical debridement and only in cases of severe infection and/or failed conservative treatment was left VAD explantation required. Since this case there has been a proposed algorithm for management of VAD-associated infections (2); our management, though prior to published guidelines, was in step with the algorithm. Of note, there was no discussion of explanting an left VAD to ECMO to aid in clearing a resistant infection. We felt this was a rational option given our inability to clear the infection. It is unclear as to exactly why our patient was never able to fully clear his infection. Given the patient’s other pre-existing extensive cardiac hardware (i.e. implanted pacer), it is possible that he remained colonized even after maximal surgical and medical therapy. Though speculative, it is possible that removing all foreign material may have allowed for complete infection clearance.
Aside from aggressive medical and surgical management, systolic heart failure with VAD-associated infections may be effectively managed with heart transplantation (9). Our consensus was that this option was neither in the best interest of the patient nor the best use of available resources given the severity of his condition.
Conclusion
Clinicians will continue to see VAD-associated infections with resistant organisms. To minimize adverse outcomes, including VAD-associated infection, prudent patient selection and timing of VAD placement is paramount, as VAD’s placed in critically ill patients have been consistently associated with adverse outcomes (10).
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- Lietz K, Long JW, Kfoury AG, Slaughter MS, Silver MA, Milano CA, Rogers JG, Naka Y, Mancini D, Miller LW. Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era: implications for patient selection. Circulation. 2007;116:497-505. [CrossRef] [PubMed]
Reference as: Gerstein NS, Chou HG, Dixon AL. Analysis of a fatal left ventricular assist device infection: a case report and discussion. Southwest J Pulm Crit Care. 2015;10:16-20. doi: http://dx.doi.org/10.13175/swjpcc139-14 PDF