Pulmonary edema after naloxone administration for opioid reversal: a systematic review of case reports and causality assessment using the Naranjo scale.

INTRODUCTION: Pulmonary edema is a rare complication occurring after naloxone administration, but the causal relationship remains insufficiently investigated. We aimed to determine the likelihood of naloxone as the causative agent in published cases of pulmonary edema. METHODS: A literature search was conducted across multiple databases, utilizing database-specific search terms such as "pulmonary edema/chemically induced" and "naloxone/adverse effects." Each case report was evaluated using the Naranjo scale, a standardized causality assessment algorithm. RESULTS: We identified 49 published case reports of pulmonary edema following naloxone administration. The median total dose of naloxone was 0.2 mg for patients presenting following a surgical procedure and 4 mg for out-of-hospital opioid overdoses. Based on the Naranjo scale, the majority of cases were classified as "possible" (n = 38) or "probable" (n = 11) adverse reactions, while no "definite" cases of naloxone-induced pulmonary edema were identified. Many patients were classified as "possible" due to limited patient information or other potential risks, such as fluid administration or airway obstruction. Forty-six of 49 patients survived (94 percent). DISCUSSION: Pulmonary edema may occur after both low and high doses of naloxone; however, low doses were primarily reported in the surgical population. Despite this complication, the majority of patients survived. Furthermore, no case report in our analysis was classified as a "definite" case of naloxone-induced pulmonary edema which limits the establishment of causality. Future studies should explore patient risk factors, including surgical versus outpatient setting and opioid-naïve versus opioid-tolerant for developing pulmonary edema and employ a causality assessment algorithm. CONCLUSIONS: These case reports suggest pulmonary edema can occur following naloxone administration, irrespective of dose. According to the Naranjo scale, there were no definite cases of naloxone-induced pulmonary edema. Overall, we suggest the benefits of naloxone administration outweigh the risks. Naloxone should be administered to treat opioid overdoses while monitoring for the development of pulmonary edema.

Phenobarbital for the Management of Alcohol Withdrawal Syndrome in Critically Ill, Surgical-Trauma Patients.

INTRODUCTION: While benzodiazepines (BZD) are the standard of care therapy for the management alcohol withdrawal syndrome (AWS), phenobarbital (PHB) is often used as an alternative agent. The objective of this study is to assess the use of PHB therapy for the management of AWS in trauma-surgical intensive care unit (TSCU) patients. MATERIALS AND METHODS: This is an institutional review board-approved single-center, retrospective study conducted at a large academic medical center. Patients aged ≥ 18 y admitted to the TSCU receiving PHB therapy for primary management of AWS were included. The primary outcome evaluated was the incidence of AWS-related complications (AWSRC) defined as severe agitation, delirium tremens, or seizures following initiation of PHB. Secondary outcomes included the incidence of oversedation and duration of mechanical ventilation. RESULTS: Sixty patients were included in this study. AWSRC following initiation of PHB occurred in 65% of patients. Median time to initiation of PHB (42 versus 18 h, P = 0.001) and rates of oversedation (79.5% versus 28.6%, P < 0.001) were significantly greater among patients who experienced AWSRC compared to those who did not. Univariate analysis revealed use of BZD therapy for ≥ 24 h prior to PHB initiation, time from hospital admission to PHB initiation ≥ 24 h, presence of AWS symptoms at baseline, and baseline MINDS score > 6 were risk factors for AWSRC. CONCLUSIONS: Delays in initiation of PHB appear to be associated with an increased risk for developing AWSRC. Further research is needed to identify an optimal dosing strategy for TSCU patients at high risk for severe AWS.

Heparin Resistance in SARS-CoV-2 Infected Patients with Venous Thromboembolism.

Introduction: Heparin resistance has been reported in coronavirus disease 2019 (COVID-19) patients receiving intravenous unfractionated heparin (IV UFH). Anti-Xa monitoring of IV UFH has been suggested over activated partial thromboplastin times due to laboratory interference from elevated factor VIII and fibrinogen levels in COVID-19 patients. Information on heparin resistance with anti-Xa monitoring in COVID-19 patients with confirmed venous thromboembolism (VTE) is lacking. Methods: In this retrospective cohort study of patients with radiographically confirmed VTE, IV UFH dosage requirements in COVID-19 positive patients were compared with COVID-19 negative patients. The primary endpoint was the IV UFH dose needed to achieve a therapeutic anti-Xa level. Secondary endpoints included time to therapeutic anti-Xa, number of dose adjustments to achieve therapeutic anti-Xa, and bleeding. Results: Sixty-four patients with confirmed VTE were included (20 patients COVID-19 positive, 44 patients COVID-19 negative). Eighty-five percent (17 of 20) of COVID-19 positive patients achieved anti-Xa ≥ 0.3 units/mL with the first anti-Xa level drawn post-IV UFH infusion initiation. The median UFH dose needed to achieve first therapeutic anti-Xa was similar between COVID-19 positive and COVID-19 negative patients (median [IQR]: 18 units/kg/hour [18-18] vs 18 units/kg/hour [18-18], P = .423). The median number of dose adjustments and time to achieve therapeutic anti-Xa were also similar between the 2 groups. The frequency of patients receiving IV UFH of more 35 000 units/day did not differ between the 2 groups. Two cases of clinically significant heparin resistance in the COVID-19 positive group were identified. Conclusions: During the first wave of COVID-19, heparin dose and time to therapeutic anticoagulation appeared to be similar between COVID-19 positive and COVID-19 negative patients monitored by anti-Xa at our institution. More studies are required to evaluate clinically significant heparin resistance in the context of the wide range of viral variants which developed, and beyond the population observed in this single center retrospective study.

Case of Severe Accidental Hypothermia Cardiac Arrest in a Subtropical Climate and Review of Management.

A patient was brought to the hospital with severe accidental hypothermia due to cold exposure associated with acute alcohol intoxication. Initial bladder core temperature was 21°C (70°F). The patient was agitated and combative with altered mental status and suffered rescue collapse during transport. Initial rhythm was ventricular fibrillation and we initiated a standard advanced cardiac life support (ACLS) protocol with rewarming measures. The patient received 28 mg of epinephrine and 13 shocks. Active and passive rewarming were initiated without extracorporeal rewarming. The patient achieved return of spontaneous circulation (ROSC) at a core temperature of 23.8°C (74.8°F). Patient was discharged 15 days later neurologically intact with no organ damage. The clinical management and implications for further research in severe accidental hypothermia management are discussed. In patients with severe accidental hypothermia (defined as <30°C or <86°F) in cardiac arrest, the optimal rewarming technique, use of epinephrine, and time when defibrillation should be attempted remain controversial. In our patient, the patient achieved ROSC in less than 2 hours with standard ACLS procedures despite a minimal increase in core temperature (21°C to 23.8°C or 70°F to 73.9°F).

Trends in multidrug-resistant gram-negative bacilli and the role of prolonged ß-lactam infusion in the intensive care unit.

Multidrug-resistant gram-negative bacilli are emerging threats in the intensive care unit setting worldwide. Extended-spectrum ß-lactamases, AmpC ß-lactamases, and carbapenem-resistant Enterobacteriaceae are increasing at an alarming rate, leaving limited therapeutic options. In addition, multidrug resistance among Pseudomonas aeruginosa and Acinetobacter baumannii has widely disseminated and become a frequent cause of nosocomial infections within many intensive care units. Therefore, resistance is increasing to all currently available antibiotics, including cephalosporins, penicillins, aztreonam, carbapenems, fluoroquinolones, and aminoglycosides. Some multidrug-resistant gram-negative bacteria remain susceptible to only a few antibiotics such as tigecycline, fosfomycin, and polymyxins. The steady trend of increasing resistance coupled with the lack of novel antibiotics targeting resistant gram-negative bacilli has forced clinicians to increasingly apply more aggressive dosing strategies, such as prolonged and continuous infusion of ß-lactam antibiotics to address the challenges associated with these difficult-to-treat pathogens. Nurses who have a thorough understanding of antibiotic resistance patterns, infection control procedures, and appropriate antibiotic use and dosing regimens, particularly the method of administration, are essential in the battle to preserve the usefulness of antibiotics and prevent further antibiotic resistance.

Intensive care unit delirium.

Intensive care unit (ICU) delirium is widespread and occurs in 20% to 80% of patients. It can be assessed with ICU-validated scoring tools. The most commonly used tools include the Confusion Assessment Method for the ICU and the Intensive Care Delirium Screening Checklist. Since ICU delirium is associated with increased morbidity and mortality, it is imperative that risk factors are identified and prevented. Risk factors include predisposing factors such as history of alcohol abuse, dementia, or hypertension and precipitating factors such as immobilization, oversedation, higher severity of illness, and use of certain psychoactive medications such as benzodiazepines. Pharmacologic treatment with atypical antipsychotics may be used to reduce the duration of delirium if prevention is not successful. However, because of the adverse effects associated with these treatments, close monitoring for side effects is warranted.