Background: Tocilizumab was approved for chimeric antigen receptor TÀcell therapy induced cytokine release syndrome and it may provide clinical benefit for selected COVIDÀ19 patients. Methods: In this retrospective cohort study, we analyzed hypoxic COVIDÀ19 patients who were consecutively admitted between March 13, 2020 and April 19, 2020. Patients with lung infiltrates and elevated inflammatory markers received a single dose of tocilizumab if no contraindication was present. Systemic steroid, hydroxychloroquine, and azithromycin were concomitantly used for majority of the patients. Findings: Of the 51 patients included for analysis, 28 (55%) received tocilizumab and 23 (45%) did not receive tocilizumab. Tocilizumab cohort required more invasive ventilation (68% vs. 22%) at baseline and during entire hospitalization (75% vs. 48%). The median time to clinical improvement in tocilizumab vs. no tocilizumab cohorts was 8 days (Interquartile range [IQR]: 6¢25 À 9¢75 days) vs. 13 days (IQR: 9¢75 À 15¢25 days) among patients who required mechanical ventilation at any time (Hazard ratio for clinical improvement: 1¢83, 95% confidence interval [CI]: 0¢57 À 5¢84) and 6¢5 days vs. 7 days among all patients (Hazard ratio for clinical improvement: 1¢14, 95% CI: 0¢55 À 2¢38), respectively. The median duration of vasopressor support and invasive mechanical ventilation were 2 days (IQR: 1¢75 À 4¢25 days) vs. 5 days (IQR: 4 À 8 days), p = 0.039, and 7 days (IQR: 4 À 14 days) vs. 10 days (IQR: 5 À 15 days) in tocilizumab vs. no tocilizumab cohorts, p = 0.11, respectively. Similar rates of hospitalÀacquired infections occurred in both cohorts (18% in tocilizumab and 22% in no tocilizumab cohort). Interpretation: In patients with severe COVID-19, tocilizumab was associated with significantly shorter duration of vasopressor support. Although not statistically significant, tocilizumab also resulted in shorter median time to clinical improvement and shorter duration of invasive ventilation. These findings require validation from ongoing clinical trials of Tocilizumab in COVIDÀ19 patients.

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Phenobarbital (PB) has been suggested as an alternative to benzodiazepines (BZD) for alcohol withdrawal (AW) management. Few studies have examined the efficacy of different PB regimens for the management of AW in the medical intensive care unit (ICU). METHODS:Retrospective, pre-post protocol, cohort study for patients with AW syndrome admitted to the medical ICU at Cleveland Clinic, Fairview Hospital, during the period from January 2019 through April 2021. Historically a symptom-triggered BZD based protocol utilizing CIWA-Ar has been employed. In September 2020, a PB-based protocol was implemented for AW management. The protocol included PB 260 mg intravenous (IV) followed by 130 mg IV repeated doses every 15 -30 minutes as needed up to a total of 15 mg/kg (ideal body weight) to maintain CIWA-Ar score below 10. We included adult patients who were admitted to medical ICU primarily for AW management. We excluded patients intubated before ICU admission or the presence of a serious medical or surgical diagnosis that would have otherwise dictated admission to the ICU. The primary outcome is ICU length of stay (LOS). Secondary outcomes include hospital LOS, intubation rate, the number of adjunctive agents, medication side effects, requirement for sitter, restraining, ICU readmission and mortality rate.RESULTS: A total of 270 patients were screened, of which only 62 patients with AW were enrolled, 15 in the PB arm and 47 in the BZD arm. Overall, 32% of all patients presented as uncomplicated AW, 42% as delirium tremens, and 13% as AW seizure. No significant differences in basic characteristics between arms were observed. Compared to BZD arm, patients who received PB had significant shorter ICU LOS (median [IQR], 28 hours [24 -37] vs 59 hours [34 -115]; P¼<.001) and hospital LOS (median [IQR] 4 days [3 -5] vs 6 days [4 -10]; P¼.006). PB arm required less number of adjunctive agents to control AW (1 [0 -1] vs 3 [2 -4]; p=<.001) including less utilization of dexmedetomidine (1 [7%] vs 22 [47%]; p=<.001). None of the patients in the PB arm required restraint use (0 vs 27 [57%]; p=<.001). No significant difference between arms with regards to medication side effects, sitter requirement, ICU readmission, intubation rate, and mortality rate. CONCLUSIONS:The initial findings from our study are suggesting that our proposed PB-AW management protocol is associated with shorter ICU and hospital LOS. It may be considered as an effective and safe alternative to BZD.CLINICAL IMPLICATIONS: Our results will help in evolving AW management guidelines in ICU.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) is the underlying cause of a global crisis that the entire world is facing. It is a highly contagious viral infection, which is why social distancing seems to be effective. Its ability to survive on various surfaces and aerosolize necessitates very meticulous precautions, including airborne isolation for severely ill patients requiring mechanical ventilation. However, these patients may need routine diagnostic investigations including chest computed tomography and chest tomography angiogram scans (CT and CTA) to rule out other potential differential diagnoses and guide management. In this case, we focus on the utility of multiorgan ultrasonography (MOU) at the bedside to diagnose and manage pulmonary embolism (PE) in COVID-19 patients.

We assessed the efficacy and safety of PB compared with benzodiazepine (BZD)-based protocols in treating AWS in MICU.DESIGN: Single-center, pre-post protocol implementation study. SETTING:The setting is a forty-bed MICU in a tertiary-level academic medical center. PATIENTS:We included all patients admitted to the MICU with a primary diagnosis of AWS. INTERVENTIONS:Intravenous PB 260 mg followed by 130-mg doses every 15-30 minutes as needed up to 15 mg/kg of ideal body weight versus escalating doses of BZD, to achieve a Clinical Institute Withdrawal Assessment Alcohol Scale-Revised score less than 10. MEASUREMENTS AND MAIN RESULTS:ICU and hospital length of stay (LOS), in addition to safety measures were the main outcomes of the study. A total of 102 patients were included, 51 in the PB arm and 51 in the BZD arm. There were no differences in baseline clinical characteristics. Half the patients in each group were admitted with delirium tremens. The use of PB-based protocol was associated with 35% reduction in median ICU LOS (1.5 d [interquartile range,; p = 0.009) and 50% reduction in hospital LOS (3 d [2.7-4 d] vs 6 d [4-10 d]; p < 0.001). After adjustment for comorbidities and clinical factors, PB protocol decreased ICU LOS days by 40% (95% CI; 25.8-53.5%). PB group required fewer adjunctive medications to control symptoms (0.7 [0.5-1] vs 2.5 [2-3]; p < 0.001), less need for intubation (1/51 [2%] vs 10/10 [19.6%]; p = 0.023) and less need for physical restraint (19/51 [37.3%] vs 29/51 [56.9%]; p = 0.047), compared with the BZD group. CONCLUSIONS:A protocol utilizing rapidly escalating doses of PB over a short period is an effective and safe alternative to BZD in treating AWS in MICU.

Background:PRES is a rare but severe condition with highly variable neurologic manifestations ranging from headaches to seizures, coma and radiologic findings of focal vasogenic edema1. It is commonly caused by hypertension, chronic renal failure, preeclampsia / eclampsia and immunosuppressants. We are reporting a rare presentation of PRES caused by severe hypercalcemia. Clinical Case: A 29- year old female presented with frontal headaches, visual disturbance, emesis and confusion. Her medical history was relevant for hyperthyroidism treated with partial thyroidectomy (on methimazole) and complicated by iatrogenic hypoparathyroidism. The resulting hypocalcemia was managed with calcitriol and calcium supplementation. On presentation, the patient was awake but disoriented. Physical examination was remarkable for right-sided hemianopsia. Admission blood pressure (BP) was 192/127 suggestive of hypertensive emergency. Initial laboratory tests revealed severe hypercalcemia (calcium: 18.7 mg/dL, ionized: 2.1 mmol/L), acute kidney injury (creatinine of 2.5 mg/dL, (baseline = &lt;1), elevated 1, 25-dihydoxy vitamin D: 65.1 pg/mL, PTH &lt;1 pg/mL, and negative urine toxicology. Head CT without contrast revealed symmetric bilateral parieto-occipital parenchymal hypoattenuation and MRI confirmed the aforementioned findings to be consistent with PRES. The patient was admitted to the ICU and started on Nicardipine intravenous (IV) infusion, IV fluids and calcitonin. Other causes of severe hypercalcemia such as multiple myeloma and hypercalcemia of malignancy were ruled out. Home calcium and calcitriol supplements were discontinued due to suspicion of intoxication. After correction of serum calcium levels her encephalopathy, hypertension and AKI resolved. She was subsequently transferred to the medical floor in stable condition. Calcium supplementation was resumed when serum calcium level normalized and calcitriol was held until further follow up of calcium levels as outpatient. Conclusion: Severe hypercalcemia is a rare cause of PRES secondary its effect on vascular smooth muscle vasoconstriction and increased vascular resistance leading to severe hypertension. Thus, it is imperative to establish a prompt diagnosis and rule out hypercalcemia in all patients presenting with PRES to prevent its devastating neurologic complications. Reference: Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015 Sep;14(9):914–925. doi: 10.1016/S1474-4422(15)00111-8. Epub 2015 Jul 13. Erratum in: Lancet Neurol. 2015 Sep;14(9):874. PMID: 26184985.

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