Venous Thromboembolism Prophylaxis in Low Body Weight Critically Ill Patients.

OBJECTIVE: To compare bleeding and thromboembolic events in low body weight patients receiving reduced-dose venous thromboembolism (VTE) prophylaxis versus standard-dose VTE prophylaxis. DESIGN: Multicenter, retrospective, cohort study. SETTING: Five Ascension Health Hospitals. PATIENTS: Adult, critically ill, low body weight (≤50 kg) patients who received either reduced-dose VTE prophylaxis (n = 140) or standard-dose VTE prophylaxis (n = 279) for at least 48 h. INTERVENTION: Reduced-dose prophylaxis (enoxaparin 30 mg daily or heparin 5000 units every 12 h subcutaneously) or standard-dose prophylaxis (enoxaparin 40 mg daily, enoxaparin 30 mg every 12 h, or heparin 5000 units every 8 h subcutaneously). MEASUREMENTS AND MAIN RESULTS: A total of 419 patients were included with a mean weight of 45.1 ± 4.2 kg in the standard-dose group and 44.0 ± 5.1 kg in the reduced-dose prophylaxis group (P = .02). The primary endpoint, composite bleeding, was significantly lower in patients receiving reduced-dose prophylaxis (5% vs 12.5%, P = .02). After adjusting for confounding factors, results remained consistent demonstrating reduced composite bleeding with reduced-dose prophylaxis (odds ratio: 0.36, 95% confidence interval: 0.14-0.96). Major bleeding events occurred in 3.6% of reduced-dose patients compared with 8.6% in standard-dose patients (P = .056). Clinically relevant nonmajor bleeding (5.4% vs 2.9%, P = .24) and VTE (2.2% vs 0%, P = .08) events were similar between groups. CONCLUSIONS: A reduced-dose VTE prophylaxis strategy in low body weight, critically ill patients was associated with a lower risk of composite bleeding and similar rate of thromboembolism.

Comparing Post-operative Opioid Consumption before and after a Patient-Controlled Analgesia Shortage: A Re-evaluation of Safety and Effectiveness.

This retrospective cohort study aimed to compare post-surgical opioid consumption before and after a PCA (patient-controlled analgesia) shortage. The study evaluated patients who received PCA vs. nurse-administered opioid analgesia (non-PCA). Two hundred and twenty-four patients ≥18 years who were initiated on analgesia within 24 h of surgery were included. The primary outcome was opioid consumption in average daily oral morphine milliequivalents (MME). The results showed that patients in the PCA group had increased MME consumption (162 ± 100.4 vs. 70.7 ± 52.8, p < 0.01), increased length of hospital stay (4.2 vs. 3.2 days, p < 0.01), and increased frequency of nausea (33 vs. 17.9%, p < 0.01). After controlling for confounding factors, the PCA group utilized significantly more opioids (84.6 MME/day, p < 0.01) than the non-PCA group. There was no difference in pain AUC/T (0.19 ± 0.07 vs. 0.21 ± 0.08, p = 0.07) and average opioid prescribing upon discharge (150 [77.5-360] vs. 90 [77.5-400], p = 0.64) between the PCA group and non-PCA group, respectively. These results question the routine use of PCA in post-operative patients due to the increased risk of opioid consumption, longer length of hospital stay, and higher incidence of nausea.

Evaluation of standard versus prolonged magnesium infusion rates in hospitalized patients: a retrospective cohort study.

BACKGROUND: Hypomagnesemia is a common electrolyte abnormality in hospitalized patients. Prolonging the infusion rate of magnesium has been hypothesized to increase retention of magnesium, however, there is limited evidence to support prolonging the rate of infusion. AIM: To compare the absolute change in serum magnesium levels from baseline to levels drawn within 24 hours after the end of infusion between two groups receiving standard or prolonged infusion. METHODS: This was a retrospective, observational cohort study comparing patients receiving magnesium infusion at a standard rate of 0.5 gm/h to those receiving magnesium infusion at a prolonged rate of 0.17 gm/h. RESULTS: Of a total of 276 patients, 138 were included in each group. No differences existed between the groups for any demographic variables (all p>0.05). The absolute change in serum magnesium level was 0.41 mg/dL versus 0.31 mg/dL in the standard and the prolonged infusion groups, respectively (p = 0.001). The length of stay after the initial magnesium dose was slightly longer with the prolonged infusion compared to the standard infusion, with a median of 2.9 days versus 3.6 days, respectively (p = 0.02). No differences existed between the groups for any secondary or safety outcomes (all p>0.05). CONCLUSION: Hospitalized general patients did not benefit from the prolonged infusion of magnesium compared to standard infusion.

Enteral Sedation in Patients Requiring Mechanical Ventilation During an Intravenous Analgesic and Sedative Shortage.

Background: There is a paucity of data evaluating the use of enteral sedation in mechanical ventilation. A sedative shortage resulted in the use of this approach. Purpose: To evaluate the feasibility of using enteral sedatives to decrease intravenous (IV) analgesia and sedative requirements. Materials/Methods: This single-center, retrospective, observational study compared two groups of patients admitted to the ICU who were mechanically ventilated. One group received a combination of enteral and IV sedatives and the second group received IV monotherapy. Linear mixed model (LMM) analyses were performed to assess the impact of enteral sedatives on IV fentanyl equivalents, IV midazolam equivalents, and propofol. Mann-Whitney U tests were performed on percent of days at goal for Richmond Agitation and Sedation Scale (RASS) and critical care pain observation tool (CPOT) scores. Results: One hundred and four patients were included. The average cohort age was 62 years and 58.7% were male. The median length of mechanical ventilation was 7.1 days and the median length of stay was 11.9 days. The LMM estimated that enteral sedatives reduced IV fentanyl equivalents received per patient by an average of 305.6 mcg/day (P = .04), although did not significantly decrease midazolam equivalents or propofol. There was no statistically significant difference in CPOT scores (P = .57 and P = .46 respectively), however RASS scores in the enteral sedation group were more often at goal (P = .03); oversedation occurred more in the non-enteral sedation group (P = .018). Conclusion: Enteral sedation may be a possible way to decrease IV analgesia requirements during periods of shortage.

Risk of bleeding with factor Xa inhibitors versus unfractionated heparin in patients with acute kidney injury.

STUDY OBJECTIVE: To compare bleeding and thromboembolic events in patients receiving therapeutic doses of apixaban or rivaroxaban versus unfractionated heparin (UFH) in patients with acute kidney injury (AKI). DESIGN: Single-center, retrospective, observational study. SETTING: Ascension St. John Hospital in Detroit, Michigan. PATIENTS: Hospitalized adult patients who received therapeutic doses of factor Xa inhibitors (n = 250) or UFH (n = 250) for at least 24 h in the setting of AKI. MEASUREMENTS AND MAIN RESULTS: After adjusting for confounding factors, patients who received a factor Xa inhibitor experienced a lower risk of composite major and clinically relevant nonmajor bleeding (CRNMB) events compared with UFH (OR: 0.57, 95% CI: 0.34-0.94; p = 0.03). There was a significantly decreased risk of CRNMB events in the factor Xa inhibitor group (OR: 0.55, 95% CI: 0.33-0.91, p = 0.02); however, no significant differences in major bleeding or venous thromboembolism (VTE) were noted. CONCLUSIONS: Our results suggest that it may be preferable to continue patients in AKI on factor Xa inhibitors versus transitioning to UFH due to the lower risk of bleeding events.

Protamine use in transcarotid arterial revascularization.

OBJECTIVE: The literature suggests that heparin reversal with protamine in transcarotid arterial revascularization (TCAR) decreases postoperative bleeding complications without an increase in stroke or death. However, the dosing of protamine in TCAR has not yet been evaluated. We aimed to evaluate our experience with intraoperative heparin reversal with protamine. METHODS: This was a single-center, retrospective, observational study that evaluated the heparin and protamine doses used during TCAR. All adult patients who underwent TCAR between 9/1/2019 and 4/2/2021 were included. Demographic data was obtained from the Vascular Quality Initiative and protamine/heparin doses were obtained from a chart review. Multivariate logistic regression models were used to assess the association between the protamine/heparin dose ratio and other variables. RESULTS: Sixty-two patients were included. The average protamine/heparin dose ratio used was 0.96 ± 0.12 mg/U; seven had a ratio less than 0.8 mg/U, and one was greater than 1.2 mg/U. Two patients experienced bleeding complications, which were managed non-operatively. No patient with a protamine/heparin ratio greater than 0.8 mg/U had postoperative bleeding. Postoperative bradycardia was observed in 32.3% of patients and hypotension in 35%, with 19% requiring vasopressors. No relationship was identified between the protamine/heparin ratio and bleeding, bradycardia, or hypotension. No 30-day myocardial infarction, stroke or death occurred. CONCLUSIONS: We identified a near 1:1 ratio of a protamine/heparin dosing regimen for the reversal of heparin during TCAR, with postoperative bleeding complications similar to those reported in the literature. However, patients who received a lower protamine/heparin ratio did not experience bleeding complications. In the era of protamine shortages, a future larger-scale study is needed to evaluate the impact of a lower protamine dose on postoperative complications.

Enoxaparin versus unfractionated heparin for venous thromboembolism prophylaxis in renally impaired ICU patients.

INTRODUCTION: Intensive care unit (ICU) patients with renal insufficiency are more likely to develop venous thromboembolism and are at an increased risk for bleeding. There is conflicting data on whether enoxaparin or unfractionated heparin (UFH) is preferred for preventing thromboembolism in this population. Therefore, the purpose of this study was to evaluate the safety of prophylactic enoxaparin versus UFH in ICU patients with renal impairment. METHODS: We conducted a single-center, retrospective cohort study of ICU patients with renal impairment who received venous thromboembolism prophylaxis with either enoxaparin or UFH. Patients were included if they were at least 18 years of age, had renal impairment (acute kidney injury, severely decreased renal function, or end-stage renal disease), and an ICU length of stay ≥72 h. The primary outcome was the proportion of patients experiencing a major bleeding event, including fatal bleed, symptomatic bleed in a critical area, or bleeding causing a ≥2 g/dl decrease in hemoglobin leading to a transfusion of ≥2 units of packed red blood cells. RESULTS: A total of 460 patients were included in the study. Of these, 231 received enoxaparin and 229 received UFH. In the unadjusted analysis, there was no difference in major bleeding events observed with enoxaparin compared to UFH (29.4% vs. 22.3%; p = 0.08) or rates of venous thromboembolism (4.3% vs. 3.5%; p = 0.64), respectively. After adjusting for confounding factors, enoxaparin showed a significant increase in major bleeding (OR: 1.84; 95% CI: 1.11 - 3.04; p = 0.02). CONCLUSION: Thromboprophylaxis with enoxaparin in critically ill patients with renal impairment was associated with an increased risk of major bleeding compared to UFH.

Dose-response of intravenous calcium in the surgical intensive care unit.

Background Hypocalcemia is common in patients admitted to the surgical intensive care unit and is associated with increased morbidity and mortality. Current dosing strategies do not always achieve ionized calcium (iCa) normalization, especially in patients with severe hypocalcemia. Objective The purpose of this study was to explore the association between intravenous (IV) calcium dose and change in ionized calcium. Setting Patients admitted to the surgical intensive care unit with concomitant hypocalcemia at a large academic hospital in the United States. Method This single center, retrospective cohort study evaluated the association between IV calcium dose and subsequent change in ionized calcium level in adult surgical intensive care unit patients with hypocalcemia. The primary outcome of this study was to develop a model exploring the association between IV calcium dose and change in iCa levels. Secondary outcomes included describing the average IV calcium dose required to normalize iCa levels, average time to normalization of iCa levels, and assessing the safety of IV calcium replacement. Main outcome measure Change in iCa. Results One hundred and ninety-four patients met study criteria. In the final model initial iCa level, total calcium dose, the interaction between initial iCa level and total calcium dose, age, and pancreatitis remained. The model (R2 = 0.625) is expressed by the following equation: Change in iCa level = 0.462 - 0.011 × [Ca dose] - 0.0007 × [Age] - 0.259 × [Initial iCa] + 0.076 × [initial iCa × Ca dose] - 0.076 × [Pancreatitis]. Removing two patients that received > 10 grams of total calcium improved the R2 to 0.769. Lastly, a simplified model removing age and pancreatitis found a similar R2 of 0.756. Conclusion We observed that change in iCa level after initial calcium dose depended on the baseline iCa. Our full and simplified model excluding two outliers predicted 76.9% and 75.6% of the variation in iCa response, respectively. If validated in other settings this model could be utilized to provide more accurate calcium dosing.

Patient controlled analgesia: The impact of an 8 versus 10 minute lockout interval in postoperative patients.

The purpose of this study was to compare the level of pain control achieved with 8 versus 10 minute lockout intervals in adult patients who received patient controlled analgesia (PCA) within 24 hours of surgery. There was no difference in pain in the first 72 hours between the 8 minute and 10 minutes group. Additionally, there was no difference in time to first PCA regimen change or a composite outcome of adverse events.

Association Between the Use of Long-Acting Insulin and Hypoglycemia in Nondiabetic Patients in the Surgical Intensive Care Unit.

PURPOSE: The purpose of this study was to examine the association between long-acting insulin and hypoglycemia in nondiabetic surgical intensive care patients. METHODS: This single-center, retrospective cohort study evaluated glycemic control in nondiabetic critically ill surgical patients receiving long-acting insulin plus sliding scale versus those receiving sliding scale alone. Patients were matched based on sliding scale order and type of surgery. The primary outcome was the proportion of patients who experienced hypoglycemia (glucose values <70 mg/dL). Secondary outcomes included comparing the distribution of glycemic events in the 2 groups and describing the proportion of patients transferred out of the intensive care unit on long-acting insulin who experienced hypoglycemia. RESULTS: One hundred twenty patients met the study criteria. Hypoglycemia was significantly higher in the long-acting insulin plus sliding scale group compared to those receiving sliding scale alone (17 [28.3%] patients vs 8 [13.3%] patients; P = .047). After adjusting for body mass index, renal failure, age, and Acute Physiology and Chronic Health Evaluation II, the odds of hypoglycemia were 4.1 times higher for patients receiving long-acting insulin and sliding scale compared to those receiving sliding scale alone ( P = .02). There were more hypoglycemic events (42 vs 20; P = .05) and hyperglycemic events (313 vs 135; P = .02) in the long-acting insulin group. CONCLUSION: This study demonstrated higher rates of hypoglycemia associated with the utilization of long-acting insulin in nondiabetic surgical intensive care patients. Risk of hypoglycemia should be weighed against possible benefits in this population.

The effect of a hypoglycemia treatment protocol on glycemic variability in critically ill patients.

INTRODUCTION: Hypoglycemia and glucose variability are independently associated with increased mortality in septic, surgical, and mixed intensive care unit (ICU) patients. Treatment of hypoglycemia with dextrose 50% can overcorrect blood glucose levels and increase glucose variability. The purpose of this study is to evaluate the effect of a hypoglycemia treatment protocol focused on minimizing glucose variability in critically ill patients. METHODS: This retrospective analysis was conducted at a 772-bed community teaching hospital in Detroit, Michigan. A standardized nursing-driven hypoglycemia treatment protocol specific to critically ill patients was implemented. Glucose variability, amount of dextrose administered, subsequent glucose monitoring, hypoglycemia recurrence, and mortality were compared between pre- and postprotocol groups. RESULTS: The coefficient of variability of blood glucose in the postprotocol group (n = 53) was decreased compared with the preprotocol group (n = 52), 40.9% versus 49.3%, respectively (P = .048). Dextrose usage was significantly reduced between groups (21.2 g preprotocol vs 11.5 g postprotocol; P < .001). The time to first blood glucose check was 36 minutes after protocol implementation compared to 61 minutes before the protocol (P = .003). Finally, the incidence of continued hypoglycemia following dextrose administration and ICU mortality was similar between groups. CONCLUSIONS: Implementation of the hypoglycemia treatment protocol described led to a reduction in glucose variability, while still providing a safe and effective way to manage hypoglycemia in critically ill patients.