Antipyretic Efficacy of Bromocriptine in Central Fever: an Exploratory Analysis.

BACKGROUND: 'Central' fevers are thought to result from disruption of hypothalamic thermoregulatory pathways following severe brain injuries. Bromocriptine, due to its central dopamine receptor agonism, has been hypothesized to have antipyretic effect in this setting. However, clinical evidence for this off-label use is limited to a few case reports. In this retrospective cohort study, we analyzed the effect of bromocriptine administration on body temperature in acute brain injury patients with suspected central fever. METHODS: We screened a cohort of adult patients that received bromocriptine in the neurologic-intensive care unit of a tertiary care hospital between January 2018 and December 2021. Indication of central fever was ascertained by review of clinical documentation. A generalized additive mixed model (GAMM) was used to model temperature as a function of time relative to bromocriptine initiation. We adjusted for potential confounding due to the following covariates: temperature recording method (invasive vs surface), concurrent antipyretic administration within 8 h, and surface cooling device use within 4 h of temperature measurement. Temperature-time function was modeled using a cubic spline with k = 10 knots. RESULTS: A total of 33 patients were included in the analysis (14 women; mean age: 50 y, standard deviation 14 y). Median dose of bromocriptine was 7.5 mg (range 2.5-40) for a median of 13 d (range 5-160). Age and sex did not impact the function of temperature over time. Predicted temperatures were significantly (p < 0.05) higher by 0.4 °C with invasive compared to surface recording methods, lower by 0.2 °C in the presence of cooling device use and lower by 0.1 °C with concurrent antipyretic use. On adjusted analysis with the GAMM, there was decline (p < 0.05) in temperature following bromocriptine initiation by - 0.3 °C at 24 h, - 0.5 °C at 48 h, and - 0.7 °C at 72 h. CONCLUSIONS: Bromocriptine use was associated with modest but statistically significant decline in temperature, with nadir at 72 h post initiation. The findings provide a data driven basis for prospective evaluation.

Refractory Heparin-Induced Thrombocytopenia in a Patient With Subarachnoid Hemorrhage-A Clinical Conundrum.

Heparin induced thrombocytopenia (HIT) often resolves with discontinuation of heparin/ heparinoid products. Severe HIT with platelet counts <20,000/µL and disseminated intravascular coagulation is frequently associated with consumptive coagulopathy and systemic thrombosis. Management of severe HIT in patients who fail to improve on discontinuing heparinoid products and argatroban infusion is not well established. We describe a patient admitted with aneurysmal subarachnoid hemorrhage (SAH) who developed severe autoimmune HIT, failed conventional anticoagulation therapy with argatroban and progressed to develop extensive deep venous thrombosis and limb ischemia. She was successfully treated using bivalirudin, immunomodulation with 2 cycles of intravenous immunoglobulin and immunosuppression with methylprednisolone. Refractory severe HIT among SAH patients is rare and pose several therapeutic challenges. We report successful treatment using alternate anticoagulant and immune suppression and modulation.

The Combination of Tocilizumab and Methylprednisolone Along With Initial Lung Recruitment Strategy in Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation: A Series of 21 Consecutive Cases.

OBJECTIVE: To describe the outcomes with use of a combination of tocilizumab and methylprednisolone administered around the time of endotracheal intubation in patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. DATA SOURCES: Retrospective chart review. STUDY SELECTION/DATA EXTRACTION: Twenty-one consecutive patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. Initial ventilator parameters were positive end-expiratory pressure 14 cm H2o and target plateau pressure 29 cm H2o to maximize lung recruitment. Methylprednisolone (125 mg every 6hr for 24 hr with tapering to 60 mg every 12 hr) was administered shortly after patients were intubated (median 11 hr after intubation). DATA SYNTHESIS: No patient in the cohort died while hospitalized (mortality, 0%; 95% CI, 0%-18%) and 18 patients have been discharged from the acute care setting. Twenty of 21 patients (95%) have been liberated from mechanical ventilation after a median duration of 8 days (range, 4-30 d). Following 48 hours of methylprednisolone, the A-a o2 gradient decreased from 455 ± 103 to 228 ± 109 mm Hg (difference 227 ± 108 mm Hg; p < 0.01). CONCLUSIONS: Our positive experience with tocilizumab in combination with methylprednisolone started early after endotracheal intubation may be one avenue for reducing the morbidity and mortality seen with severe coronavirus disease 2019 and merits further exploration in clinical studies.

Managing Nonoperable Intracranial Bleeding Associated With Apixaban: A Series of 2 Cases.

OBJECTIVE: To report 2 cases of nonoperable intracranial bleeding associated with apixaban managed by 3-factor prothrombin complex concentrate (PCC3). CASE SUMMARIES: Case 1 presented with a 1.3-cm left parieto-occipital hemorrhage and a thin subdural hematoma (SDH) on the left tentorium of the brain about 6 hours after his last dose of apixaban. Case 2 presented with a 4-mm left parafalcine SDH with time of most recent apixaban dose unknown. The patients received 24.9 to 25.5 U/kg of PCC3 with none to 1 U fresh frozen plasma (FFP) and demonstrated minimal or no progression in lesions measured by repeat computed tomography (CT) after treatment. One patient was discharged to a skilled nursing facility after 8 days; the other patient was discharged to home after 18 days. DISCUSSION: Apixaban has no specific antidote. Current bleeding management strategies are based on expert opinion. The risks and benefits for differing strategies are unclear, and little clinical experience for managing apixaban-associated intracranial bleeding has been reported to date. These cases describe the clinical use of PCC3 to manage parieto-occipital and subdural hemorrhage associated with apixaban in events not requiring surgical intervention. CONCLUSION: In these 2 cases, 25 U/kg PCC3, with none to one unit FFP, ceased apixaban-associated intracranial bleeding without apparent thrombogenic complications.

Prophylactic Acid-Suppressive Therapy in Hospitalized Adults: Indications, Benefits, and Infectious Complications.

Acid-suppressive therapy for prophylaxis of stress ulcer bleeding is commonly prescribed for hospitalized patients. Although its use in select, at-risk patients may reduce clinically significant gastrointestinal bleeding, the alteration in gastric pH and composition may place these patients at a higher risk of infection. Although any pharmacologic alteration of the gastric pH and composition is associated with an increased risk of infection, the risk appears to be highest with proton pump inhibitors, perhaps owing to the potency of this class of drugs in increasing the gastric pH. With the increased risk of infection, universal provision of pharmacologic acid suppression to all hospitalized patients, even all critically ill patients, is inappropriate and should be confined to patients meeting specific criteria. Nurses providing care in critical care areas may be instrumental in screening for appropriate use of acid-suppressive therapy and ensuring the drugs are discontinued upon transfer out of intensive care or when risk factors are no longer present.

Nasal Methicillin-Resistant Staphylococcus aureus (MRSA) PCR Testing Reduces the Duration of MRSA-Targeted Therapy in Patients with Suspected MRSA Pneumonia.

The objective of this study was to evaluate the impact of pharmacist-ordered methicillin-resistant Staphylococcus aureus (MRSA) PCR testing on the duration of empirical MRSA-targeted antibiotic therapy in patients with suspected pneumonia. This is a retrospective analysis of patients who received vancomycin or linezolid for suspected pneumonia before and after the implementation of a pharmacist-driven protocol for nasal MRSA PCR testing. Patients were included if they were adults of >18 years of age and initiated on vancomycin or linezolid for suspected MRSA pneumonia. The primary endpoint was the duration of vancomycin or linezolid therapy. After screening 368 patients, 57 patients met inclusion criteria (27 pre-PCR and 30 post-PCR). Baseline characteristics were similar between the two groups, with the majority of patients classified as having health care-associated pneumonia (68.4%). The use of the nasal MRSA PCR test reduced the mean duration of MRSA-targeted therapy by 46.6 h (74.0 ± 48.9 h versus 27.4 ± 18.7 h; 95% confidence interval [CI], 27.3 to 65.8 h; P < 0.0001). Fewer patients in the post-PCR group required vancomycin serum levels and dose adjustment (48.1% versus 16.7%; P = 0.02). There were no significant differences between the pre- and post-PCR groups regarding days to clinical improvement (1.78 ± 2.52 versus 2.27 ± 3.34; P = 0.54), length of hospital stay (11.04 ± 9.5 versus 8.2 ± 7.8; P = 0.22), or hospital mortality (14.8% versus 6.7%; P = 0.41). The use of nasal MRSA PCR testing in patients with suspected MRSA pneumonia reduced the duration of empirical MRSA-targeted therapy by approximately 2 days without increasing adverse clinical outcomes.

Impact of an Analgesia-Based Sedation Protocol on Mechanically Ventilated Patients in a Medical Intensive Care Unit.

BACKGROUND: Recent attention to adverse effects of intensive care unit (ICU) sedation has led to the use of strategies that target a "lighter" depth of sedation. Among these strategies are "analgosedation" protocols, which prioritize pain management and preferentially use IV opioids before administration of continuously infused sedatives such as propofol or midazolam. We hypothesized that using an analgosedation protocol would result in a shorter duration of mechanical ventilation than a protocol with greater emphasis on IV sedatives METHODS: : We conducted a retrospective study comparing the duration of mechanical ventilation before and after implementation of an analgosedation protocol in a 24-bed medical ICU. Patients were aged 18 years or older and required mechanical ventilation where a light level of sedation was clinically appropriate. Exclusion criteria included a clinical need for deeper levels of sedation or tracheal intubation confined to the perioperative period. RESULTS: Seventy-nine patients were included in the postimplementation group and 65 in the preimplementation group. After adjustment for baseline covariates, introduction of the 2013 analgosedation protocol was associated with a decreased duration of mechanical ventilation (-26.62 hours; 95% confidence interval, - 44.98 to -8.26, P = 0.005). Patients managed with the analgosedation protocol experienced a lighter level of sedation (median Richmond Agitation-Sedation Scale, -2.57 vs -1.25, P = 0.001) and improved pain management (median Critical-Care Pain Observation Tool score, 2.0 vs 1.5, P = 0.03). The use of continuously infused sedatives was reduced by 54.3% (92.3% vs 38.0%, P < 0.001). CONCLUSIONS: Our findings suggest that implementation of an analgosedation protocol was associated with an overall lighter level of sedation, shorter mean ventilator duration, and a reduced use of continuous infusion sedatives. Further studies are needed to assess the impact of such protocols on ICU delirium.

Ebola virus disease: roles and considerations for pharmacists.

Ebola virus disease (EVD) poses significant clinical care implications for pharmacists. Emergency preparedness efforts should be undertaken to ensure vital response to EVD. Pharmacists should consider factors such as enhanced use of resources for front-line EVD patient care along with procurement of investigational medications. Appropriate and timely preparation, distribution, and administration of treatment for patients with EVD in the setting of substantial critical illness as well as infection control measures are essential. Aggressive supportive care and early, goal-directed therapy are cornerstones of therapy, whereas investigational treatments for EVD will likely play a larger, more well-defined role as future clinical trials are conducted.

Nasal methicillin-resistant Staphylococcus aureus polymerase chain reaction: a potential use in guiding antibiotic therapy for pneumonia.

CONTEXT: The role at admission of nasal polymerase chain reaction (PCR) for patients with methicillin-resistant Staphylococcus aureus (MRSA) in guiding antibiotic therapy for lower respiratory tract infection is unknown. OBJECTIVE: To determine whether nasal MRSA PCR at admission can predict the absence of MRSA in lower respiratory tract secretions. DESIGN: We performed a retrospective study of adult patients admitted to a large urban hospital. Patients had a nasal MRSA PCR test and a lower respiratory tract culture obtained within 48 hours of admission and the culture yielded S aureus. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values. RESULTS: Our results showed high sensitivity (93.3%) and negative predictive value (95.2%) of nasal PCR for MRSA in the lower respiratory tract. CONCLUSION: With its high sensitivity and negative predictive value, a nasal MRSA PCR test performed within 48 hours of hospital admission could help guide the discontinuation of MRSA-directed empiric antibiotic therapy in patients who are unlikely to be infected with this organism. A prospective study is needed to confirm these findings.