Effectiveness of an Intravenous Insulin-Based Treatment Protocol for the Management of Hypertriglyceridemia-Associated Acute Pancreatitis.

Background: There is burgeoning interest in intravenous insulin for hypertriglyceridemia-induced acute pancreatitis (HTG-AP) as a less invasive alternative to plasmapheresis; however, there are few published descriptions of disease-specific insulin protocols. Objective: To compare the efficacy and safety of an insulin infusion-based protocol with nonstandardized medical therapy for HTG-AP. Methods: This is a retrospective analysis before and after creation of an HTG-AP-specific insulin infusion treatment protocol. Inclusion criteria were age ≥18 years, an initial triglyceride level >1000 mg/dL, and a diagnosis of AP. The primary outcome of the study was time to a triglyceride level ≤1000 mg/dL. Results: Sixty-seven patients were included in this study (26 pre-protocol and 41 in the HTG-AP insulin protocol group). Baseline characteristics between the groups were similar, with median initial triglyceride levels >3500 mg/dL. There was a trend toward patients treated with the HTG-AP-specific infusion reaching a triglyceride level ≤1000 mg/dL faster (43.3 [24.9-72.1] vs 26.9 [17.7-51.1] hours; P = 0.07). Those treated to ≤500 mg/dL achieved this faster with the disease-specific infusion (49.2 [29.4-67.8] vs 70.9 [36.3-107.2] hours, P = 0.04). Hypoglycemia was numerically lower in the HTG-AP-specific insulin infusion group despite higher insulin infusion rates (7.3% vs 19.2%). No patient in the HTG-AP-specific protocol group required plasmapheresis. Conclusions: The use of an HTG-AP-specific insulin infusion protocol, compared with antecedent nonstandardized care, resulted in prompter achievement of a triglyceride level ≤500 mg/dL and a strong trend toward faster achievement of ≤1000 mg/dL without an increased risk of hypoglycemia. While intravenous insulin may be considered the initial medical therapy for HTG-AP, further studies are needed to determine the optimal dosing.

A Review of the Evidence for Corticosteroids in COVID-19.

OBJECTIVE: To review available evidence on corticosteroids in acute respiratory distress syndrome (ARDS), Coronavirus Disease 2019 (COVID-19), and other viral pneumonias. DATA SOURCES: A literature search of MEDLINE, PubMed and clinicaltrials.gov was performed to identify studies between 1980 to 2020 using the following search terms: corticosteroids, COVID19, severe respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and influenza. Pre-printed articles were also reviewed at medRxiv.org. DATA ANALYSIS: Corticosteroids were not recommended early in the COVID-19 pandemic outside of the use for concomitant indications (i.e. ARDS, septic shock) as they have been associated with delayed time to viral clearance in other viral pneumonias. A randomized trial showed a mortality benefit with dexamethasone in COVID-19. Guidelines have been updated to include a strong recommendation for their use in COVID-19 in those hospitalized requiring supplemental oxygen or mechanical ventilation. CONCLUSION: Based on data from available randomized trials, patients that require respiratory support or mechanical ventilation benefit from corticosteroid therapy. Corticosteroids are an inexpensive and readily available therapy that should be standard of care in hospitalized COVID-19 patients requiring respiratory support.

Probable drug-drug interaction between dabigatran and quinidine resulting in thrombin time rebound despite multiple idarucizumab doses.

: Dabigatran is a direct thrombin inhibitor that was approved as an alternative to warfarin because it offers the benefit of predictable pharmacokinetic properties, favorable safety profile and ease of administration. Despite the improved safety profile, dabigatran use can lead to bleeding events. The bleeding risk associated with dabigatran is higher in the setting of renal impairment or drug-drug interactions resulting in supratherapeutic serum concentrations. Unfortunately, clinically significant interactions are not always identified by providers, especially in the case of infrequent drug-drug combinations. Dabigatran-related coagulopathy can be effectively reversed by idarucizumab. However, high dabigatran serum concentrations can lead to increased tissue distribution resulting in decreased idarucizumab efficacy and repeat idarucizumab doses may be warranted. This case describes a patient presenting with uncontrolled bleeding due to a significant drug-drug interaction between quinidine and dabigatran resulting in acute kidney injury and persistent coagulopathy despite multiple idarucizumab doses and transfusion measures.

Hepatorenal Acute Kidney Injury and the Importance of Raising Mean Arterial Pressure.

BACKGROUND: The efficacy of vasoconstrictors in hepatorenal syndrome (HRS) is variable. We hypothesized that the effectiveness of vasoconstrictor therapy in improving kidney function ultimately relates to the magnitude of the achieved mean arterial pressure (MAP) increase. METHODS: A retrospective study was conducted to identify cirrhotic individuals treated with vasoconstrictors for acute kidney injury (AKI) presumably caused by HRS to examine the relationship between change in MAP and change in serum creatinine (sCr) using multivariate mixed linear regression. RESULTS: Among 73 patients treated with midodrine/octreotide, change in MAP inversely correlated with change in sCr (p = 0.0005). The quartile with the greatest increase in MAP (+15.9 to +29.4 mm Hg) was associated with a subsequent absolute decrease in sCr. The strength of the correlation increased when the analysis was restricted to those who met the HRS criteria (n = 27, p = 0.002), where the third (+5.3 to +15.6 mm Hg) and fourth (+15.9 to +20.9 mm Hg) quartiles of MAP change were associated with a decrease in sCr. A similar but stronger correlation was found among 14 patients treated with norepinephrine either after failing midodrine/octreotide (n = 10) or de novo (n = 4; p = 0.002), where a rise in MAP of +19.2 to 25 mm Hg was associated with a larger reduction in sCr. Associations remained significant after adjustment for baseline parameters. CONCLUSIONS: The magnitude of MAP rise during HRS therapy with midodrine/octreotide or norepinephrine correlated with a reduction in sCr concentration. Our results suggest that achieving a pre-specified target of MAP increase might improve renal outcomes in hepatorenal AKI.

Statins and delirium: is there a role?

Delirium is a serious but potentially avoidable complication in critically ill patients. Various pathophysiological processes have been associated with delirium development; however, neuroinflammation hypothesis and pleiotropic effects are the reasons why HMG-CoA reductase inhibitors have been evaluated for delirium prevention. Statin therapy is associated with favorable outcomes in critically ill patients, but significant variability of results exists in patients who received these agents postoperatively. Study design methodological weaknesses, inconsistent delirium assessment, and lack of information on sedation regimens may have confounded these outcomes. Furthermore, no evidence exists on the type of statin, lipophilic or non-lipophilic, that is associated with the most benefit or when therapy with a statin should be initiated. Thus, the efficacy of HMGM-CoA reductase inhibitors on delirium prevention has not been fully established and non-pharmacological methods should remain mainstay of therapy.