Melissa L. Thompson Bastin

Effects of Etomidate on Adrenal Suppression: A Review of Intubated Septic Patients

Background Etomidate is a commonly used sedative during rapid sequence intubation (RSI). Septic patients are at an increased risk of independently developing adrenal suppression, which has been associated with increased mortality in some studies. Since etomidate affects cortisol production, its use in septic patients is controversial. However, data are still lacking to prove that etomidate should be avoided in this patient population. Objectives The objective was to review patients diagnosed with sepsis who received etomidate during RSI. Our hypothesis is that patients who receive etomidate will experience clinically significant hypotension within the first 24 hours of intubation. Methods A retrospective cohort study was conducted on patients intubated in the emergency department (ED) and medical/surgical floors at our institution from 2004 to 2010. Once patients with a diagnosis of sepsis were identified, it was determined whether the patients received etomidate or a different sedative during intubation. The primary endpoint was clinically significant hypotension: systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg. Results One hundred fifty-seven patients, 110 etomidate and 47 non-etomidate, were included in the final analysis. Hypotension was seen in 79 (71.8%) patients who received etomidate and in 14 (29.8%) patients who received another sedative (P ≤ .001). There were no statistically significant differences in secondary objectives. Conclusion Etomidate use for induction of anesthesia during RSI was associated with clinically significant hypotension when compared to other sedatives. The hypotension was transient and did not translate into statistically significant differences in the secondary clinical endpoints.

Comparison of High-Dose Versus Standard Dose Oseltamivir in Critically Ill Patients With Influenza.

Background: Limited data support high-dose oseltamivir in critically ill patients with influenza. In several recent influenza seasons, there were oseltamivir drug shortages. Methods: This was a retrospective cohort analysis of 57 patients admitted to the intensive care unit (ICU) with confirmed influenza. Patients receiving high-dose oseltamivir were compared to those receiving standard dosing. Results: When adjusted for clinically relevant predictors of disease severity, including age, duration of therapy, Acute Physiology and Chronic Health Evaluation II score, and receipt of extracorporeal membrane oxygenation, there was no difference in the duration of mechanical ventilation, oxygenation, ICU length of stay, or hospital length of stay between the high-dose and standard dose groups. Conclusions: As compared to the standard doses of oseltamivir, higher-dose (ie, double dose) oseltamivir was not associated with improvement in any clinical outcomes. Using higher doses empirically on all patients during influenza season may exacerbate local drug shortages.

Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy.

Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patients actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

Oseltamivir Dosing in Critically Ill Patients With Severe Influenza

Objective: To evaluate the literature for published reports regarding the efficacy of standard versus higher dosing of oseltamivir in critically ill patients with severe influenza. Data Sources: An English-language literature search was conducted using MEDLINE (1966-February 2014) using the terms oseltamivir and influenza limited to humans and adults older than 19 years. Additional articles were identified through a manual search of the references obtained from the MEDLINE search. Study Selection and Data Extraction: Articles were manually screened for inclusion related to pharmacokinetic or clinical studies comparing varying doses of oseltamivir, particularly in the critically ill patient population. Studies investigating the pharmacokinetics of oseltamivir in continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) were also included. Data Synthesis: During the 2009 H1N1 influenza pandemic, the World Health Organization suggested 150 mg twice daily as a consideration in critically ill patients with severe influenza. The basis for the recommendation can be traced back to animal studies investigating the H5N1 virus. Three different studies in humans investigating higher doses in severe influenza have found no differences in clinical outcomes between standard and higher dosing. Pharmacokinetic studies suggest adequate absorption in critically ill patients. Although no dosage adjustment appears to be needed for ECMO patients, reduction may berequired for CRRT.. Conclusions:. Although additional data are needed for a definitive conclusion, the small body of literature available in humans does not support routine use of high-dose oseltamivir in critically ill patients.

Vitamin C in Sepsis: When It Seems Too Sweet, It Might (Literally) Be

References 1. Dugan KC, Laxmanan B, Murgu S, Hogarth DK. Management of persistent air leaks. Chest. 2017;152(2):417-423. 2. Petrella F, Rizzo S, Radice D, et al. Predicting prolonged air leak after standard pulmonary lobectomy: computed tomography assessment and risk factors stratification. Surgeon. 2011;9(2):72-77. 3. Liang S, Ivanovic J, Gilbert S, et al. Quantifying the incidence and impact of postoperative prolonged alveolar air leak after pulmonary resection. J Thorac Cardiovasc Surg. 2013;145(4):948-954. 4. Chahla M, Larson CD, Parekh KR, et al. Transpleural ventilation via spiracles in severe emphysema increases alveolar ventilation. Chest. 2016;149(6):e161-e167. 5. Khauli S, Bolukbas S, Reed RM, Eberlein M. Interlobar collateral ventilation in severe emphysema. Thorax. 2016;71(12):1168-1169.

Hypoxemia associated with nimodipine in a patient with an aneurysmal subarachnoid hemorrhage

PURPOSE A case of probable nimodipine-induced hypoxemia in a patient undergoing treatment for aneurysmal subarachnoid hemorrhage (SAH) is reported. SUMMARY A 62-year-old man hospitalized for SAH developed symptoms of respiratory distress on several occasions within days of initiation of nimodipine therapy (60 mg every four hours, with three doses withheld during intubation for intracranial surgery). Several hours after extubation (on hospital day 5), the patient had rapidly worsening tachypnea and declining arterial oxygen saturation (SPO2) despite increased oxygen delivery by mask, necessitating reintubation. When a nurse noted that the declines in SPO2 occurred soon after nimodipine administration, the patients respiratory and hemodynamic functions were closely monitored after a single dose of nimodipine via nasogastic tube; the monitoring results supported the suspicion that nimodipines vascular effects were a causal or contributory factor in the hypoxemia episodes. With subsequent fractionated dosing (30 mg every two hours), the patient completed the prescribed 21-day course of nimodipine therapy. Using the rating scale of Naranjo et al., this case was assigned a score of 7, indicating a probable pulmonary adverse reaction to nimodipine. As nimodipine is commonly used in cases of SAH to reduce delayed neurologic deficits due to persistent cerebral vasospasm, clinicians should be mindful of its potential hypoxemic effects in vulnerable patients. CONCLUSION A patient with aneurysmal SAH developed hypoxemia associated with the administration of nimodipine. Hypoxemia is a known complication of treatment with other vasodilatory agents, particularly in patients who have concomitant pulmonary disease.

Hemodynamic Instability Secondary to Vasopressin Withdrawal in Septic Shock

Rationale: Vasopressors such as norepinephrine are first line for support of mean arterial pressure (MAP) in the management of septic shock. Their use, however, is commonly associated with many adverse events. These detriments frequently trigger the use of alternative, noncatecholamine therapies, including vasopressin. Vasopressin deficiency is a known physiologic consequence of septic shock, and while guidelines recommend vasopressin in addition to norepinephrine, no consensus exists on the duration of deficiency or ideal time of cessation. Studies have suggested that vasopressin discontinuation prior to other vasopressors may lead to hypotension; however, data are limited. This study evaluates the optimal sequence for the discontinuation of vasopressin therapy in septic shock. Methods: This was a 1-year retrospective study of 152 patients admitted to the medical intensive care unit (ICU) with septic shock who received concurrent norepinephrine and vasopressin for vasoactive support. Patients were excluded if death occurred on vasopressors, within 24 hours after discontinuation of vasopressors, or within 48 hours of ICU admission. The primary outcome of hemodynamic instability included incidence of hypotension after vasopressor discontinuation (2 consecutive MAPs < 60 mm Hg), fluid bolus administration, greater than 0.05 μg/kg/min increase in norepinephrine requirements, or addition of an alternative vasopressor. Secondary outcomes included time to hypotension, total vasopressor duration, arrhythmias, mortality, and length of stay. Results: Ninety-one patients met exclusion criteria, resulting in 61 patients for evaluation. Vasopressin was the first vasoactive therapy to be discontinued in 19 patients and last in 42 patients. Baseline characteristics and the use of potentially confounding treatments known to effect MAP were similar between groups. Discontinuation of vasopressin first was associated with a significant increase in hemodynamic instability (74% vs 16.7%, P < .01), with a shorter time to hemodynamic instability (5 vs 15 hours, P < .01). Secondary outcomes were similar. Conclusion: Vasopressin discontinuation prior to cessation of norepinephrine infusion was associated with an increased risk of hemodynamic instability.

Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy

OBJECTIVES The aim of this review was to evaluate current literature for dosing recommendations for the use of antiepileptic medications in patients receiving renal replacement therapy (RRT). DATA SOURCES With the assistance of an experienced medical librarian specialized in pharmacy and toxicology, we searched MEDLINE, EMBASE, CINAHL, Web of Science, WorldCat, and Scopus through May 2016. STUDY SELECTION AND DATA EXTRACTION Four hundred three articles were screened for inclusion, of which 130 were identified as potentially relevant. Micromedex® DRUGDEX as well as package inserts were used to obtain known pharmacokinetic properties and dosage adjustment recommendations in RRT if known. DATA SYNTHESIS Data regarding antiepileptic drug use in RRT are limited and mostly consist of case reports limiting our proposed dosing recommendations. Known pharmacokinetic parameters should guide dosing, and recommendations are provided where possible. CONCLUSION Additional studies are necessary before specific dosing recommendations can be made for most antiepileptic drugs in critically ill patients receiving RRT, specifically with newer agents.

Use of Continuous Renal Replacement Therapy for Removal of Dabigatran in a Patient in Need of Emergent Surgery

Purpose. To report the ability to remove serum dabigatran using continuous renal replacement therapy (CRRT) in a patient with life-threatening bleeding. Summary. A 77-year-old female with history of atrial fibrillation who takes dabigatran for stroke prevention presented with abdominal pain. Patient was found to have bleeding and possible mesenteric ischemia and was taken to the operating room and had continued bleeding postoperatively. CRRT was initiated for the removal of any remaining dabigatran, with serum dabigatran levels collected to evaluate removal of dabigatran with CRRT. This patient had an increased dabigatran level prior to intervention, which decreased to an undetectable level after use of CRRT. Greater than 80% of the drug was removed due to 4 hours of CRRT and residual kidney function. Reversal of dabigatran is an area of current research with recent FDA approval of idarucizumab for use. Conclusion. Bleeding may occur as a result of the use of dabigatran and change in patients clinical condition. Use of CRRT may be an option in removing serum dabigatran in the case of a life-threatening bleed.

Preceptor development: Responses to frequently asked questions from preceptors in academic hospitals.

Preceptor development continues to be a trending topic within our profession. ASHP’s accreditation standards include requirements for preceptor development, and residency program directors continue to seek novel and unique methods for developing preceptors’ aptitude and ability for teaching.[1][