Acute Amiodarone Pulmonary Toxicity.

Amiodarone is an effective antiarrhythmic that frequently is used during the perioperative period. Amiodarone possesses a significant adverse reaction profile. Amiodarone-induced pulmonary toxicity (AIPT) is among the most serious adverse effects and is a leading cause of death associated with its use. Despite significant advances in the understanding of AIPT, its etiology and pathogenesis remain incompletely understood. The diagnosis of AIPT is one of exclusion. The clinical manifestations of AIPT are categorized broadly as acute, subacute, and chronic. Acute AIPT is a rarer and more aggressive form of the disease, most often encountered in cardiothoracic surgery. Acute respiratory distress syndrome (ARDS) is the predominating pattern of amiodarone's acute pulmonary toxicity. The incidence, risk factors, pathogenesis, and diagnosis of acute AIPT are speculative. Early cardiothoracic literature investigating AIPT often attributed amiodarone to the development of postoperative ARDS. Subsequent studies have found no association between amiodarone and acute AIPT and ARDS development. As a drug that is frequently prescribed to a patient population deemed most at risk for this fatal disease, the conflicting evidence on acute AIPT needs further investigation and clarification.

Very High-Dose Furosemide Continuous Infusions: A Case Series.

BACKGROUND: There is paucity of data evaluating the efficacy and safety of very high-dose furosemide continuous infusions (≥40 mg/h) for volume removal. This infusion is a novel strategy of loop diuretic administration that may add valuable data to current literature. METHODS AND RESULTS: This was a retrospective chart review. Patients were eligible for inclusion if prescribed a very high-dose furosemide infusion (defined as ≥40 mg/h, up to 240 mg/h) from April 1, 2017, to January 1, 2019, at Thomas Jefferson University Hospital. Data collected included the change in cumulative urine output, net urine output, incidence of acute kidney injury, occurrences of hypotension, electrolyte abnormalities, body weight, and ototoxicity. Twenty-two patients were included in this analysis. The median change in 24-hour urine output from before to after very high-dose continuous furosemide infusion increased from 1193 mL at 24 hours before infusion initiation to 3518 mL at 24 hours after infusion initiation (P < .01). Serum creatinine increased 24 hours after infusion initiation but decreased within 48 hours. There were no electrolyte abnormalities. Out of 22 patients, only 2 had an occurrence of hypotension. No patients were reported to have ototoxicity. CONCLUSIONS: Very high-dose furosemide continuous infusions provide a significant increase in diuresis without worsening renal function, disturbing electrolytes, or increasing the risk of ototoxicity. Further studies are necessary to examine the efficacy and safety of this novel strategy.

Pharmacokinetics of Ketamine at Dissociative Doses in an Adult Patient With Refractory Status Asthmaticus Receiving Extracorporeal Membrane Oxygenation Therapy.

PURPOSE: First-line management of severe asthma exacerbations include the use of inhaled short-acting ß-agonists, anticholinergics, and systemic corticosteroids. Continuous intravenous ketamine given at dissociative doses may be a pharmacologic option in patients who are intubated with life-threatening severe bronchospasm unresponsive to standard therapy. We describe the case of a 44-year-old man admitted to the intensive care unit for status asthmaticus requiring intubation and mechanical ventilation. METHODS: The patient developed severe refractory hypercapnic respiratory failure necessitating additional respiratory support with veno-venous extracorporeal membrane oxygenation (ECMO) therapy. Ketamine treatment was initiated at 0.5 mg/kg/h continuous infusion on the day of admission for pain control and required up-titration to 2 mg/kg/h by intensive care unit day 4 for bronchodilation. Whole blood samples were obtained for pharmacokinetic analysis of ketamine during ECMO. FINDINGS: The plasma concentration at steady state was 1018.7 ng/mL, with an estimated clearance of 1.96 L/kg/h after up-titration. The Vd was 14.18 L/kg, the ke was 0.14 hr-1, and the t½ was 5 hours. IMPLICATIONS: Compared with healthy adults, there was a 6.5-fold increase in the Vd. However, the Vd was similar compared with critically ill patients not receiving ECMO. Further studies should focus on the effect of ECMO on ketamine pharmacokinetic properties.

Medication Complications in Extracorporeal Membrane Oxygenation.

The need for extracorporeal membrane oxygenation (ECMO) therapy is a marker of disease severity for which multiple medications are required. The therapy causes physiologic changes that impact drug pharmacokinetics. These changes can lead to exposure-driven decreases in efficacy or increased incidence of side effects. The pharmacokinetic changes are drug specific and largely undefined for most drugs. We review available drug dosing data and provide guidance for use in the ECMO patient population.

Clinical and economic impact of substituting dexmedetomidine for propofol due to a US drug shortage: examination of coronary artery bypass graft patients at an urban medical centre.

BACKGROUND: Propofol has reduced healthcare costs in coronary artery bypass graft (CABG) surgery patients by decreasing post-operative duration of mechanical ventilation. However, the US shortage of propofol necessitated the use of alternative agents. OBJECTIVE: This study sought to evaluate clinical and economic implications of substituting dexmedetomidine for propofol in patients undergoing CABG surgery. METHODS: This was a retrospective cohort study. Patients undergoing isolated, elective CABG surgery and sedated with either propofol or dexmedetomidine during the study period were included. The cohorts were matched 1:1 based on important characteristics. The primary outcome was the number of patients achieving a post-operative duration of mechanical ventilation ≤6 h. Secondary outcomes were post-operative intensive care unit (ICU) length of stay (LOS) ≤48 h, total post-operative LOS ≤5 days, the need for adjunctive opioid therapy and associated cost savings. Variables recorded included patient demographics, co-morbid medical conditions, health risks, sedation drug doses, post-operative medical complications and sedation-related adverse events. Univariate and multivariate analyses were completed to examine the relationship between these covariates and post-operative LOS. The cost analysis consisted of examination of the net financial benefit (or cost) of choosing dexmedetomidine versus propofol in the study population, with utilisation observed in the study converted to costs using institutional data from the Premier database. RESULTS: Eighty-four patients were included, with 42 patients per cohort. Mechanical ventilation duration ≤6 h was achieved in 24 (57.1 %) versus 7 (16.7 %) in the dexmedetomidine and propofol cohorts, respectively (p < 0.001). More patients treated with dexmedetomidine achieved ICU LOS ≤48 h (p < 0.05) and total hospital LOS ≤5 days (p < 0.05), as compared with the propofol group. Multivariate analysis revealed that having one or more post-operative medical complication was the most significant predictor of increased post-operative LOS, whereas choosing dexmedetomidine was also significant in terms of reduced post-operative LOS. The estimated net financial benefit of choosing dexmedetomidine versus propofol was US$2,613 per patient (year 2012 value). CONCLUSIONS: Findings suggest that use of dexmedetomidine as an alternative to propofol for sedation of CABG patients post-operatively contributes to reduced mechanical ventilation time, ICU LOS and post-operative LOS. Higher drug costs resulting from the propofol shortage were offset by savings in post-operative room and board costs. Additional savings may be possible by preventing medical complications to the extent possible.

US Propofol Drug Shortages: A Review of the Problem and Stakeholder Analysis.

BACKGROUND: Drug shortages have increased in recent years in the United States, with a majority involving sterile injectable drugs. Propofol, a sterile injectable drug, is frequently used as a sedative, thanks to its rapid onset of action and a short recovery period. However, propofol is complicated and expensive to manufacture, and recent events involving major manufacturers have led to shortages of the drug in the United States. OBJECTIVES: To review the events leading to the shortage of propofol and to discuss how the shortage is affecting various healthcare stakeholders, as an example of the systemwide problem of drug shortages in the United States. DISCUSSION: Manufacturers currently have little economic incentive to produce propofol, a generic drug whose production is costly and carries a high liability. The enforcement of good manufacturing practices by the US Food and Drug Administration is beneficial for the safety of US citizens, but it can inherently lead to a sudden halt in the manufacturers' production of drugs. Hospitals are affected because they must develop a plan to address current and potential shortages, including restricting the use of medications that have a shortage and shifting to alternative agents. CONCLUSION: The shortage of propofol significantly impacted the delivery of care in the United States in 2009, and various stakeholders are working to increase the existing supply of propofol and to investigate the use of alternative medications when the supply runs short. The case of propofol presented in this article is used to illustrate a systemwide view of the impact of drug shortages on the US healthcare system.