Factors associated with bleeding after ultrasound-assisted catheter-directed thrombolysis for the treatment of pulmonary embolism.

Ultrasound-assisted catheter directed thrombolysis (US-CDT) is frequently used for the treatment of pulmonary embolism. Due to the variety of thrombolytic and anticoagulant dosing utilized in practice, patients with pulmonary embolism who undergo US-CDT may be at an increased risk of bleeding. The primary objective of this study was to determine factors associated with major bleeding occurring with US-CDT. Secondary outcomes included in-hospital mortality and ventilator-free days. This multicentre retrospective cohort study evaluated inpatients diagnosed with pulmonary embolism and treated with US-CDT and systemic anticoagulation. A total of 173 patients were included. Most patients receiving US-CDT had a submassive pulmonary embolism with a median Pulmonary Embolism Severity Index (PESI) score of 85. Major bleeding events occurred in 37 of the 173 patients (21%). In-hospital mortality occurred in four (11%) of the patients who experienced major bleeding and three (2%) patients who did not experience major bleeding (P = 0.04). Factors associated with a higher risk of major bleeding included female sex and anticoagulation strategy. The odds of major bleeding were 3.3 times higher for women than for men (odds ratio = 3.32, 95% confidence interval 1.29-8.54). In addition, for each second increase in goal aPTT the odds of major bleeding increased by 5% (odds ratio = 1.05, 95% confidence interval 1.02-1.09). In patients with pulmonary embolism treated with US-CDT, major bleeding may be underestimated. In this analysis, major bleeding was associated with female sex and higher goal aPTT levels. In addition, bleeding with US-CDT was associated with a higher risk of in-hospital mortality.

Effect of desmopressin acetate on acute spontaneous intracranial hemorrhage in patients on antiplatelet therapy.

PURPOSE: To evaluate the impact of desmopressin acetate (DDAVP) on poor outcomes, hematoma expansion, and adverse events in patients diagnosed with a non-traumatic, antiplatelet-associated intracranial hemorrhage (ICH). METHODS: This was a multicenter, retrospective, propensity-matched cohort study comparing DDAVP to control in patients diagnosed with a non-traumatic ICH previously on antiplatelet therapy. Notable exclusion criteria included admission to trauma service, subarachnoid hemorrhages, confounding coagulopathic factors, and hematoma evacuation. Poor outcome, defined as discharge to hospice or in-patient mortality, was the primary outcome. Secondary outcomes included intracranial hematoma expansion and occurrence of adverse events, which included hyponatremia and thromboembolic events. RESULTS: A total of 49 patients receiving DDAVP were compared to 107 controls in the unmatched cohort. Thirty-seven patients treated with DDAVP and 55 controls were included in the propensity-matched analysis, which was adjusted for age, ethnicity, history of diabetes, receipt of platelet transfusion, and thromboembolism prophylaxis. Poor outcome (16.2% DDAVP vs 29% control, p = 0.13), rates of hematoma expansion (11.8% DDAVP vs 11.1% control, p = 0.99), and adverse events (21.6% DDAVP vs 20% control, p = 0.99) were statistically similar between the matched groups. CONCLUSIONS: DDAVP administration in patients with spontaneous antiplatelet-associated ICH was not associated with a reduction in poor outcomes, hematoma expansion, or an increase in adverse events. Use of DDAVP in this patient population appears to be safe. Larger prospective studies are warranted to evaluate DDAVP utility in this patient population.

Impact of Clinical Sepsis Phenotypes on Mortality and Fluid Status in Critically Ill Patients.

BACKGROUND: Sepsis is associated with high rates of in-hospital mortality, despite being the focus of medical research and public health initiatives for several years. The primary objective of this study was to determine the influence of septic phenotypes on rates of in-hospital mortality throughout intensive care unit (ICU) admission. PATIENTS AND METHODS: Retrospective, single-center cohort study. Medical ICU of an academic medical center. Medical ICU patients admitted between January 2016 and August 2019 with a "sepsis alert" were screened for admitting diagnosis of "sepsis" or "septic shock." Patients were classified into one of four clinical sepsis phenotypes: multi-organ failure (MOF), respiratory dysfunction (RD), neurologic dysfunction (ND), or other patients (OP). RESULTS: An analysis of 320 patients was completed. In-hospital mortality was different between groups (P < 0.001). Patients with the MOF phenotype had the highest rate of mortality (48.4%), followed by the ND phenotype (39.7%), RD phenotype (20.8%), and OP phenotype (13.7%). There were differences in volume balances between phenotypes at 48 h (P = 0.001), 72 h (P < 0.001), and 96 h (P < 0.001) after hospital presentation, with the MOF and ND phenotypes having the largest volume balances at these time points. Ventilator-free days (P < 0.001) and ICU length of stay (LOS) (P = 0.030) were different between groups. There was no difference in hospital LOS (P = 0.479). CONCLUSIONS: This data supports the presence of marked intra-disease differences in septic patient presentation and correlation with clinical outcomes including mortality. Additionally, significantly more positive fluid balances were observed between survivors and non-survivors in some patient subsets. Using pragmatic clinical variables readily available to providers to classify patients into septic phenotypes has the propensity to guide treatment strategies in the future.

An Association Between Hyperchloremia and Acute Kidney Injury in Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: While an association between hyperchloremia and worse outcomes, such as acute kidney injury and increased mortality, has been demonstrated in hemorrhagic stroke, it is unclear whether the same relationship exists after acute ischemic stroke. This study aims to determine the relationship between moderate hyperchloremia (serum chloride ≥115 mmol/L) and acute kidney injury in patients with ischemic stroke. METHODS: This is a multicenter, retrospective, propensity-matched cohort study of adults admitted for acute ischemic stroke. The primary objective was to determine the relationship between moderate hyperchloremia and acute kidney injury, as defined by the Acute Kidney Injury Network criteria. Secondary objectives included mortality and hospital length of stay. RESULTS: A total of 407 patients were included in the unmatched cohort (332 nonhyperchloremia and 75 hyperchloremia) and 114 patients (57 in each group) were matched based upon propensity scores. In the matched cohort, hyperchloremia was associated with an increased risk of acute kidney injury (relative risk 1.91 [95% confidence interval 1.01-3.59]) and a longer hospital length of stay (16 vs 12 days; P = .03). Mortality was higher in the hyperchloremia group (19.3% vs 10.5%, P = .19), but this did not reach statistical significance. CONCLUSIONS: In this study, hyperchloremia after ischemic stroke was associated with increased rates of acute kidney injury and longer hospital length of stay. Further research is needed to determine which interventions may increase chloride levels in patients with acute ischemic stroke and the association between hyperchloremia and clinical outcomes.

Effect of Alteplase Administration on International Normalized Ratio in Patients With Acute Ischemic Stroke.

BACKGROUND/OBJECTIVE: Alteplase may elevate international normalized ratio (INR) results, although the exact rate of elevation occurrence is not firmly established in the literature. The purpose of this study is to determine the occurrence rate of INR elevation following alteplase administration. We also aimed to determine what factors are independently associated with the development of elevated INR following alteplase administration for ischemic stroke. METHODS: We conducted a multicenter, retrospective, cohort study of patients who received alteplase for acute ischemic stroke. Patients were screened for baseline INR measurement and a repeat value within 24 hours of alteplase administration. The primary outcome was the percent of patients who experienced ≥0.4-point increase in INR. Secondary outcomes included the rate of adverse bleeding events and identification of factors independently associated with elevated INR following alteplase administration. RESULTS AND CONCLUSIONS: Two hundred and sixty-one patients were included, with 44 (16.9%) patients having an INR increase of 0.4 or more. Patients with an INR increase ≥0.4 experienced a nonstatistically significant increase in bleeding episodes (8.8% vs 18.2%; P = .10). We identified African American race (odds ratio, 3.48, 95% confidence interval, 1.5-7.6; P = .002) as an independent predictor of INR increase ≥0.04. An INR elevation is common following receipt of alteplase for ischemic stroke. Those of African American race were at increased risk of INR elevation; however, more studies are needed to determine whether these patients are at a higher bleeding risk as a result of INR elevation.

Use of Intraventricular Medications in Critically Ill Patients: A Systematic Review.

New evidence and increased use of intracranial devices have increased the frequency of intraventricular (IVT) medication administration in the neurologic intensive care unit. Significant benefits and risks are associated with administration of medications directly into the central nervous system. This review summarizes important literature, along with key information for clinicians regarding the administration, dosing, monitoring, and adverse effects related to IVT medication usage. Multiple medications have supporting literature for their use in critically ill patients including amphotericin B, aminoglycosides, colistimethate, daptomycin, quinupristin/dalfopristin, vancomycin, alteplase, and nicardipine. Sterile preparation and delivery, along with different types of devices that support medication administration, are also reviewed. One randomized, placebo-controlled trial of alteplase demonstrated decreased mortality but no change in good functional outcome. Other reports of IVT medication use are mainly limited to case reports and retrospective case series. There is a need for increased research on the topic; however, several practical barriers decrease the likelihood of a large, placebo-controlled, prospective study for most indications. Providers should consider implementing protocols to maximize safety of IVT medication delivery to ensure optimal patient outcomes.

Adjusted versus actual body weight dosing of 4-factor prothrombin complex concentrate in obese patients with warfarin-associated major bleeding.

The package insert of 4-factor prothrombin complex concentrate (4F-PCC) contains specific dosing recommendations stating to determine the patients dose based on their INR and weight, capping the weight at 100 kg. However, the mean body mass index (BMI) in the 4F-PCC U.S. approval study was 27 kg/m2, and there is a lack of literature identifying the ideal dosing strategy in obesity. We conducted a retrospective analysis of obese patients (BMI ≥ 30 kg/m2) who received 4F-PCC for warfarin associated emergent bleeding reversal. Treatment groups were those that received 4F-PCC on adjusted body weight (AdjBW) and those on actual body weight (ActBW). The primary outcome was the percent of patients achieving coagulopathy reversal, defined as a post-treatment INR < 1.4 for neurologic indications and < 1.5 for all others. A total of 78 obese patients were included (28 AdjBW and 50 ActBW). Baseline INR (3.1 vs. 2.8; p = 0.052) and BMI (33.6 vs. 33.6 kg/m2) were similar between groups. Achievement of goal INR was significantly lower in the AdjBW group (36% vs. 68%; p = 0.006). A majority of patients had intracranial hemorrhage (32% vs. 54%; p = 0.06), and the median dose of 4F-PCC was lower in the AdjBW group (2120 vs. 2500 units; p = 0.02). Dosing 4F-PCC using adjusted body weight in obese patients resulted in a significantly lower rate of coagulopathy reversal. ActBW should be used to dose 4F-PCC in obese patients when the 100 kg dose cap is utilized per the package insert recommendations.

Impact of Moderate Hyperchloremia on Clinical Outcomes in Intracerebral Hemorrhage Patients Treated With Continuous Infusion Hypertonic Saline: A Pilot Study.

OBJECTIVES: Hyperchloremia has been associated with increased morbidity and mortality in critically ill patients. While previous research has demonstrated an association between hypertonic saline and hyperchloremia, limited data exist in neurocritical care patients. The objective of this study is to determine the impact of moderate hyperchloremia (chloride ≥ 115 mmol/L) on clinical outcomes in intracerebral hemorrhage patients treated with continuous IV infusion 3% hypertonic saline. DESIGN: Multicenter, retrospective, propensity-matched cohort study. SETTING: Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and comprehensive stroke center designation. PATIENTS: Intracerebral hemorrhage patients discharged between September 2011 and September 2015 were evaluated and matched 1:1 based on propensity scoring. INTERVENTIONS: Continuous IV infusion 3% hypertonic saline. MEASUREMENTS AND MAIN RESULTS: A total of 219 patients were included in the unmatched cohort (143 moderate hyperchloremia and 76 nonhyperchloremia) and 100 patients in the propensity-matched cohort. In-hospital mortality was significantly higher in those who developed moderate hyperchloremia in a propensity-matched cohort (34% vs 14%; p = 0.02). Moderate hyperchloremia independently predicted in-hospital mortality in multivariable logistic regression analysis (odds ratio, 4.4 [95% CI, 1.4-13.5]; p = 0.01). CONCLUSIONS: We observed higher rates of in-hospital mortality in patients who developed moderate hyperchloremia during treatment with continuous IV infusion 3% hypertonic saline, with moderate hyperchloremia independently predicting in-hospital mortality. These results suggest that chloride values should be monitored closely during hypertonic saline treatment as moderate elevations may impact outcomes in intracerebral hemorrhage patients.

Predictors of Acute Kidney Injury in Neurocritical Care Patients Receiving Continuous Hypertonic Saline.

BACKGROUND AND PURPOSE: Continuous intravenous 3% hypertonic saline (HTS) infusions are commonly used for the management of cerebral edema following severe neurologic injuries. Despite widespread use, data regarding the incidence and predictors of nephrotoxicity are lacking. The purpose of this study was to describe the incidence and identify predictors of acute kidney injury (AKI) in neurocritical care patients administered continuous infusion HTS. METHODS: This was an institutional review board-approved, multicenter, retrospective cohort study of patients receiving HTS infusions at 2 academic medical centers. A univariate analysis and multivariable logistic regression were used to identify predictors of AKI. Data regarding AKI were evaluated during treatment with HTS and up to 24 hours after discontinuation. RESULTS: A total of 329 patients were included in our analysis, with 54 (16%) developing AKI. Those who developed AKI experienced significantly longer stays in the intensive care unit (14.8 vs 11.5 days; P = .006) and higher mortality (48.1% vs 21.9%; P < .001). We identified past medical history of chronic kidney disease (odds ratio [OR]: 9.7, 95% confidence interval [CI]: 1.9-50.6; P = .007), serum sodium greater than 155 mmol/L (OR: 4.1, 95% CI: 2.1-8.0; P < .001), concomitant administration of piperacillin/tazobactam (OR: 3.9, 95% CI: 1.7-9.3; P = .002), male gender (OR: 3.2, 95% CI: 1.5-6.6; P = .002), and African American race (OR: 2.6, 95% CI: 1.3-5.2; P = .007) as independent predictors of AKI. CONCLUSION: Acute kidney injury is relatively common in patients receiving continuous HTS and may significantly impact clinical outcomes.

Clinical utility of methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction assay in critically ill patients with nosocomial pneumonia.

PURPOSE: This study investigated the diagnostic performance characteristics of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) assay in critically ill patients with nosocomial pneumonia. MATERIALS AND METHODS: This retrospective, single-center study included adult patients admitted to an intensive care unit with suspected nosocomial pneumonia. Patients must have received an MRSA nasal PCR assay and respiratory culture within predetermined time intervals. The primary outcome included the diagnostic performance characteristics of the assay. Secondary outcomes included the change in negative predictive value (NPV) over time, rate of acute kidney injury, and cost avoidance associated with vancomycin and monitoring. RESULTS: In 400 patients meeting inclusion criteria, the prevalence of culture confirmed MRSA pneumonia was 9.3%. When compared to initial cultures, the PCR assay demonstrated 91.89% sensitivity and 84.3% specificity with a positive predictive value and NPV of 37.36% and 99.03%. The NPV decreased to 87.5% at 21.9 days. No difference was found in rates of acute kidney injury. A cost avoidance of $108 per patient was estimated in patients de-escalated based on negative results. CONCLUSION: In critically ill patients, an MRSA nasal PCR assay has a high NPV for nosocomial pneumonia and can be used to guide vancomycin de-escalation.

Safety of Continuous Peripheral Infusion of 3% Sodium Chloride Solution in Neurocritical Care Patients.

BACKGROUND: Numerous drug information resources recommend that continuous intravenous 3% sodium chloride solution be administered via a central catheter. OBJECTIVES: To evaluate the incidence of infusion-related reactions and electrolyte abnormalities in neurocritical care patients treated with continuous intravenous infusion of 3% sodium chloride solution via a peripheral catheter. METHODS: Data on patients treated with continuous intravenous infusion of 3% sodium chloride solution at 2 academic medical centers were evaluated retrospectively to determine the administration site. Electronic notes on catheter status were reviewed to determine the occurrence of infusion-related reactions. Prespecified thresholds were used to assess electrolyte abnormalities. RESULTS: Of 213 patients who had peripheral continuous intravenous infusions of 3% sodium chloride solution, 15 (7%) had infusion-related reactions. Administration was changed to a central catheter in 56 patients (26.3%), but only 5 changes were due to an infusion-related reaction. Most (157 patients, 73.7%) received their entire treatment peripherally, for a median duration of 44 hours, 3 minutes. The most common electrolyte abnormalities were hyperchloremia in 49.3% and hypokalemia in 46.9% of patients. CONCLUSION: Current recommendations that a central catheter is required for continuous intravenous infusion of 3% sodium chloride solution should be reevaluated. Only a few patients who had peripheral infusions had infusion-related reactions. Electrolyte abnormalities occurred frequently with peripheral infusion, but the clinical importance of the abnormalities remains unclear.

3-Factor Versus 4-Factor Prothrombin Complex Concentrate for Warfarin Reversal in Severe Bleeding: A Multicenter, Retrospective, Propensity-Matched Pilot Study.

Current guidelines recommend 4-factor prothrombin complex concentrate (4PCC) for emergent reversal of bleeding secondary to warfarin. While current research has demonstrated superiority of 4PCC over plasma, direct comparisons with 3-factor PCC (3PCC) are lacking. The purpose of this study is to compare the efficacy and safety of 3PCC and 4PCC. We conducted a retrospective analysis of patients who received PCC at one of four medical centers. All patients in the 3PCC group were treated at one center that utilizes a fixed, weight-based dosing protocol. After evaluation of all patients meeting inclusion criteria, propensity-score matching was used to adjust for differences in treatment characteristics. There was no difference in the primary outcome of INR ≤ 1.4 between 3PCC and 4PCC in both the unmatched (85.7 vs. 90.6 %; p = 0.37) and matched (84.2 vs. 92.1 %; p = 0.48) analyses. There was a significant difference in goal INR achieved favoring 4PCC (56.3 vs 90.0 %; p < 0.02) when baseline INR > 4.0. A total of three thrombotic events were documented, all in the 4PCC group. We found no difference in the rate of INR reversal in those treated with 3PCC and 4PCC. However, those with a baseline INR > 4.0 may experience more successful INR reversal with 4PCC.

The impact of endocrine supplementation on adverse events in septic shock.

PURPOSE: The objective of this study was to compare the incidence of severe adverse events of vasopressin vs hydrocortisone for endocrine support therapy in patients with septic shock. MATERIALS AND METHODS: This was a retrospective, propensity-matched cohort of patients admitted to the medical intensive care unit with septic shock between February 2012 and February 2015. Patients were included if vasopressin or hydrocortisone was administered for hemodynamic support secondary to norepinephrine. RESULTS: In the unmatched cohort of 124 patients, vasopressin was associated with a significant decrease in the number of severe adverse events (P=.03). In the matched cohort, severe adverse events occurred 3 times as often in patients receiving hydrocortisone; however, this difference was not statistically significant. (odds ratio, 3.33; 95% confidence interval, 0.92-12.11; P=.06). In the matched cohort, vasopressin was associated with a faster time to hemodynamic stability (P<.05) and discontinuation of hemodynamic support (P<.01) with an increased requirement for third-line therapy (P<.01). No statistical differences were seen in length of stay (intensive care unit and hospital), length of mechanical ventilation, and in-hospital mortality. CONCLUSION: Given the lower incidence of adverse events and faster time to hemodynamic stability, vasopressin appears to be the most advantageous endocrine agent for hemodynamic support in septic shock.

Major publications in the critical care pharmacotherapy literature: January-December 2013.

PURPOSE: Ten recently published articles with important implications for critical care pharmacotherapy are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group is a national assembly of experienced intensive care unit (ICU) pharmacists across the United States. Group members monitor 25 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on (1) applicability to critical care practice, (2) relevance to pharmacy practitioners, and (3) quality of evidence or research methodology. Hundreds of relevant articles were evaluated by the group during the period January-December 2013, of which 98 were summarized and disseminated nationally to CCPLU group members. Among those 98 publications, 10 deemed to be of particularly high utility to critical care practitioners were included in this review. The 10 articles address topics such as rapid lowering of blood pressure in patients with intracranial hemorrhage, adjunctive therapy to prevent renal injury due to acute heart failure, triple-drug therapy to improve neurologic outcomes after cardiac arrest, and continuous versus intermittent infusion of ß-lactam antibiotics in severe sepsis. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2013, including an updated guideline on the management of myocardial infarction and reports on advances in research focused on improving outcomes in patients with stroke or cardiac arrest and preventing the spread of drug-resistant pathogens in the ICU.

A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients.

OBJECTIVE: Dexmedetomidine and propofol are commonly used sedatives in neurocritical care as they allow for frequent neurologic examinations. However, both agents are associated with significant hemodynamic side effects. The primary objective of this study is to compare the prevalence of severe hemodynamic effects in neurocritical care patients receiving dexmedetomidine and propofol. DESIGN: Multicenter, retrospective, propensity-matched cohort study. SETTING: Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and board-certified neurointensivists. PATIENTS: Neurocritical care patients admitted between July 2009 and September 2012 were evaluated and then matched 1:1 based on propensity scoring of baseline characteristics. INTERVENTIONS: Continuous sedation with dexmedetomidine or propofol. MEASUREMENTS AND MAIN RESULTS: A total of 342 patients (105 dexmedetomidine and 237 propofol) were included in the analysis, with 190 matched (95 in each group) by propensity score. The primary outcome of this study was a composite of severe hypotension (mean arterial pressure < 60 mm Hg) and bradycardia (heart rate < 50 beats/min) during sedative infusion. No difference in the primary composite outcome in both the unmatched (30% vs 30%, p = 0.94) or matched cohorts (28% vs 34%, p = 0.35) could be found. When analyzed separately, no differences could be found in the prevalence of severe hypotension or bradycardia in either the unmatched or matched cohorts. CONCLUSIONS: Severe hypotension and bradycardia occur at similar prevalence in neurocritical care patients who receive dexmedetomidine or propofol. Providers should similarly consider the likelihood of hypotension or bradycardia before starting either sedative.

Predictors of severe hypotension in neurocritical care patients sedated with propofol.

INTRODUCTION: Propofol is used extensively in neurocritical care (NCC) due to its pharmacologic properties allowing for facilitation of serial neurologic examinations. Despite widespread use, few studies have identified risk factors for hypotension in these patients. We aimed to determine predictors of hypotension in NCC patients sedated with propofol. METHODS: This retrospective, multicenter study evaluated 237 patients at two academic medical centers, both with dedicated NCC teams led by board-certified neurointensivists. Univariate analyses were performed to determine risk factors associated with severe hypotension during sedation with propofol. Multivariable analysis was performed to determine variables independently associated with hypotension, defined as a mean arterial pressure (MAP) less than 60 mmHg. RESULTS: There was an average maximum reduction in MAP of 28.8 % after propofol initiation in the entire cohort. Severe hypotension developed in 62 (26.2 %) patients to a median nadir MAP of 56 mmHg. Those who developed severe hypotension had a longer median duration of mechanical ventilation (5.0 vs. 3.6 days; p = 0.01) and an increased in-hospital mortality (38.7 vs. 24.0 %; p = 0.03). Multivariable logistic regression analysis identified increasing number of changes to the propofol infusion rate, baseline MAP 60-70 mmHg, and need for renal replacement therapy (RRT) as factors independently associated with hypotension. CONCLUSIONS: Multiple factors predicted hypotension in NCC patients receiving propofol. Clinicians should use propofol cautiously in patients with a lower baseline MAP or receiving RRT. Development of protocols related to the frequency of dose titrations is also recommended to prevent this avoidable complication.