The Risk of Major Bleeding With Apixaban Administration in Patients With Acute Kidney Injury.

BACKGROUND: Apixaban is eliminated by the kidneys and in acute kidney injury (AKI) there is potential for an increase in apixaban exposure and bleeding events. In one instance, data have shown higher than normal bleed risk in patients with AKI, unless calibrated anti-factor Xa monitoring is used, which is not widely available. OBJECTIVE: To evaluate bleeding with apixaban administration to hospitalized patients with an AKI in an unmonitored real-world scenario. METHODS: We conducted a retrospective study of patients admitted to a large urban academic teaching hospital from April 2015 to March 2022, who received apixaban for venous thromboembolism or nonvalvular atrial fibrillation (NVAF). The primary outcome evaluated major bleeding when apixaban was administered to patients with or without an AKI. RESULTS: A total of 232 patients were evaluated (116 per group). Most patients (79.7%) were on apixaban for NVAF, 32.7% had chronic kidney disease, 58.2% were on a medication increasing bleed risk, and HAS-BLED score was a median of 2 in both groups. No differences were noted between groups for bleeding (AKI group 7.8% vs non-AKI 3.4%; P = 0.15), and on regression analysis, coadministration of a P2Y12 inhibitor was predictive of major bleeding (odds ratio = 5.9; 95% confidence interval = 1.4-23.6). CONCLUSION AND RELEVANCE: Although no differences between groups were noted, apixaban use in the AKI group resulted in a higher than normally reported incidence of apixaban-associated major bleeding, and concomitant antiplatelet use increased bleed risk as well. Cautious use of apixaban and further investigation with larger studies are warranted in this area.

The Effect of Vancomycin and Piperacillin-Tazobactam on Incidence of Acute Kidney Injury in Patients With Obesity.

Background: Increasing evidence suggests that administration of combination vancomycin and piperacillin-tazobactam (VPT) increases the incidence of acute kidney injury (AKI) beyond that of vancomycin alone. But these investigations have not evaluated AKI risk specifically in an increasingly prevalent obese population in whom VPT pharmacokinetics are altered. Objective: To evaluate AKI risk with VPT administration to patients with obesity. Methods: We conducted a multicenter retrospective study of obese patients admitted to 2 separate academic teaching hospitals from January 2010 to December 2021, who received VPT, or vancomycin plus either cefepime, meropenem, or ceftazidime. The primary outcome evaluated AKI when patients were treated with or without VPT. Results: A total of 227 patients were evaluated (114 in VPT, vs 113 in control group). Overall, body mass index (35.6 kg/m2 ± 4.8vs 36.1 kg/m2 ± 5.2; P = .44) was similar between the VPT and control groups respectively. Total vancomycin dose on day 1 of antibiotic therapy (3,432 mg ± 935 vs 2,732 mg ± 912; P < .01) and nephrotoxin administration (75.4% vs 62.8%; P = .04) were higher in the VPT group. Incidence of AKI was higher in the VPT group (37.7%vs 14.2%; P = .01) and on regression analysis VPT was predictive of developing AKI (OR = 3.9; 95% CI = 2.0-7.7; P < .01). Conclusion and Relevance: In this retrospective study, the incidence of AKI was increased in obese patients receiving therapy with VPT. Vancomycin combination therapy with ceftazidime, cefepime, and meropenem appeared to be safe and was associated with less nephrotoxicity. Cautious use of VPT and further investigation with larger studies are warranted in this area.

The Association of Elevated Lactate With Multiple Vasopressor Administration in Patients With Septic Shock: A Retrospective Cohort Study.

Purpose: In patients with septic shock and elevated lactate, there is limited evidence evaluating supplementary vasopressor use beyond vasopressin (AVP) and norepinephrine (NE). The purpose of this study is to describe vasopressor utilization and clinical outcomes based on lactate level. Methods: We conducted a retrospective study of patients with septic shock requiring NE. Patients were divided into 2 groups: baseline lactate level of ≥4 mmol/L (lactate group) or <4 mmol/L (control group). The primary outcome was supplementary utilization of AVP, phenylephrine (PE), epinephrine, and dopamine, in addition to background NE therapy between the 2 patient groups. Results: A total of 100 patients in each group were included. Mean baseline lactate was 7.6 mmol/L and 2.3 mmol/L in the study and control groups, respectively (P < .01). Combination therapy with NE plus AVP (55% vs 26%; P < .01), NE plus PE (26% vs 3%; P < .01), and NE, AVP, plus PE (17% vs 0%; P < .01) was more common in the lactate group. On regression analysis, lactate group was a predictor of using AVP (OR 3.0; 95% CI 1.6-5.9), PE (OR 7.5; 95% CI 2.1-26.7), and AVP plus PE (OR 11.1; 95% CI 2.5-49.7). Conclusions: In this small retrospective study, multiple vasopressor use was high in patients with severely elevated lactate. The optimal vasopressor regimen in this patient population needs further investigation.

Safety of Propofol When Used for Rapid Sequence Intubation in Septic Patients: A Multicenter Cohort Study.

Purpose: Septic patients are at risk for hypotension, and this risk may increase during rapid sequence intubation (RSI). Sedatives such as propofol must be used carefully due to its ability to reduce vascular sympathetic tone. Since the safety of propofol for RSI is not well described in sepsis, this was a study evaluating propofol and its effects on hemodynamics when used for RSI in a septic population. Materials and methods: We conducted a multicenter, retrospective, cohort study of patients with sepsis or severe sepsis requiring sedation for RSI. Patients receiving a propofol bolus for RSI were compared to patients undergoing RSI without a propofol bolus. The safety profile of propofol was evaluated according to the rates of post-intubation hypotension and vasopressor utilization between groups. Results: A total of 179 patients (79 propofol, 100 non-propofol) were evaluated. There were no differences in hypotension (81% vs 78%; P = .62) or vasopressor utilization between the propofol and non-propofol groups (43% vs 49%; P = .43). Patients in the non-propofol group had increased APACHE II scores and healthcare-associated infections. Conclusions: In this cohort study, administration of propofol for RSI in patients with sepsis and severe sepsis did not increase incidence of hypotension or vasopressor use, but acute illness may have introduced provider selection bias causing less propofol use in the non-propofol group. Larger prospective studies are needed to better characterize the adverse hemodynamic effects of propofol, before propofol bolus doses for RSI can be considered for safe use in this population.

The Effect of Prearrest Acid-Base Status on Response to Sodium Bicarbonate and Achievement of Return of Spontaneous Circulation.

BACKGROUND: The efficacy of sodium bicarbonate (SB) administration during in-hospital cardiac arrest (IHCA) for treatment of acidosis is not well described. The available literature has only evaluated out-of-hospital arrest events in patients with suspected acidosis caused by prolonged arrest. OBJECTIVE: This study evaluated SB and its effects on return of spontaneous circulation (ROSC) in patients experiencing IHCA, based on presence of acidosis at baseline as determined by prearrest bicarbonate levels. METHODS: We conducted a retrospective cohort study of patients who all received intravenous SB during IHCA. Patients with prearrest bicarbonate levels >21 mmol/L (nonacidotic group) were compared with those with prearrest bicarbonate levels ≤21 mmol/L (acidotic group) for the primary outcome of ROSC. RESULTS: A total of 225 patients (102 acidotic, 123 nonacidotic) were evaluated. Asystole (37.3% vs 34.1%; P = 0.63) and pulseless electrical activity (30.4% vs 29.3%; P = 0.85) were the most common presenting rhythms. There were no differences in ROSC in the overall population (53.9% vs 48.8%; P = 0.44) or between those who had early (within 20 minutes) or delayed (after 20 minutes) ROSC. Secondary outcomes, including cardiopulmonary resuscitation duration, epinephrine administration, and total SB, were similar between groups. CONCLUSIONS AND RELEVANCE: In this cohort study, administration of SB for IHCA in patients with prearrest acidosis was not associated with increased incidence of ROSC compared with those without prearrest acidosis. Our data suggest that there may be no benefit to the administration of SB in the setting of IHCA, regardless of prearrest acidotic status. Further investigation into the effect of SB for treatment of acidosis in IHCA is warranted.

The effect of obesity on the rate of heparin-induced thrombocytopenia.

: Heparin-induced thrombocytopenia (HIT) occurs in patients receiving heparin-containing products due to the formation of platelet-activating antibodies to heparin and platelet factor 4. Diagnosis includes utilization of a scoring system known as the 4-T score, and HIT laboratory assays. Recently, obesity was identified as a potential factor associated with the development of HIT. The objective of this study was to evaluate the association of HIT with obesity in ICU and general medicine patients. We performed a chart review of adult patients within the Methodist Healthcare System, and included patients who had an ELISA and serotonin release assay laboratory tests reported within same hospital admission in which they also had documented receipt of heparin. Obese patients were compared with nonobese patients (BMI < 30) for the primary outcome of HIT occurrence, and secondary outcomes including rate of thrombosis, 4-T scores, and ELISA optical density values. We also generated a 5-T score by including one additional point for those with a BMI of 30 or more to determine the predictive value of this score in identifying HIT. Obesity was confirmed to be a risk factor for HIT, and the 5-T score model was also predictive of the development of HIT. However, the 5-T score was not statistically more predictive of HIT than the 4-T score. Predicting HIT remains challenging and novel markers of HIT are needed to improve HIT recognition. Although obesity did not improve the 4-T score, it may improve the predictability of other scoring systems, and further investigation is warranted.

Impact of Admission Hypertension on Rates of Acute Kidney Injury in Intracerebral Hemorrhage Treated with Intensive Blood Pressure Control.

BACKGROUND: Current guidelines recommend that rapid systolic blood pressure (SBP) lowering to 140 mmHg may be considered in intracerebral hemorrhage (ICH) patients regardless of initial SBP. However, limited safety data exist in patients presenting with varying degrees of severe hypertension. The purpose of this study was to determine whether there was an increased risk of acute kidney injury (AKI) based upon degree of presentation hypertension in ICH patients whose blood pressure was reduced intensively. METHODS: This retrospective, cohort study evaluated ICH patients treated with intensive blood pressure control (SBP ≤140 mmHg) who presented with three degrees of presentation hypertension: mild (SBP 141-179 mmHg), moderate (SBP 180-219 mmHg), and severe (SBP ≥ 220 mmHg). Univariate analysis of demographics variables, ICH severity, and factors known to impact AKI was conducted between the three groups. Post hoc testing was used to compare differences between specific groups, with a Bonferroni correction adjusting for multiple comparisons. Additionally, we conducted logistic regression analysis to determine whether baseline SBP group independently predicted AKI. RESULTS: We included 401 patients (177 with mild, 124 with moderate, and 100 with severe hypertension). There was a significant increase in the prevalence of AKI between groups, with the severe group experiencing the highest rate (p < 0.001). The presence of severe hypertension was also found to independently predict AKI development (odds ratio 2.6; p < 0.001). CONCLUSION: Our study observed higher rates of AKI in patients presenting with severe hypertension. Further research is needed to determine the most appropriate strategies for managing blood pressure in ICH patients presenting with higher SBP.

Continuous Infusion Antiepileptic Medications for Refractory Status Epilepticus: A Review for Nurses.

Status epilepticus requires treatment with emergent initial therapy with a benzodiazepine and urgent control therapy with an additional antiepileptic drug (AED) to terminate clinical and/or electrographic seizure activity. However, nearly one-third of patients will prove refractory to the aforementioned therapies and are prone to a higher degree of neuronal injury, resistance to pharmacotherapy, and death. Current guidelines for refractory status epilepticus (RSE) recommend initiating a continuous intravenous (CIV) anesthetic over bolus dosing with a different AED. Continuous intravenous agents most commonly used for this indication include midazolam, propofol, and pentobarbital, but ketamine is an alternative option. Comparative studies illustrating the optimal agent are lacking, and selection is often based on adverse effect profiles and patient-specific factors. In addition, dosing and titration are largely based on small studies and expert opinion with continuous electroencephalogram monitoring used to guide intensity and duration of treatment. Nonetheless, the doses required to halt seizure activity are likely to produce profound adverse effects that clinicians should anticipate and combat. The purpose of this review was to summarize the available RSE literature focusing on CIV midazolam, pentobarbital, propofol, and ketamine, and to serve as a primer for nurses providing care to these patients.

Effects of propofol on vasopressor use in patients with sepsis and severe sepsis: A pilot study.

PURPOSE: Propofol is one of the most commonly used sedatives in the intensive care unit (ICU) despite its undesirable hypotensive effects. The purpose of this study was to determine the effects of continuous intravenous (CIV) propofol on vasopressor requirements in mechanically ventilated patients with sepsis. MATERIALS AND METHODS: A multicenter, retrospective, propensity-matched pilot study was conducted comparing patients with sepsis or severe sepsis who received CIV propofol for sedation to those who did not. The primary outcome was incidence of vasopressor support. Secondary outcomes included change in mean arterial pressure, mortality, and length of stay. RESULTS: A total of 279 patients (149 CIV propofol, 130 non-CIV propofol) were evaluated, with 174 patients matched 1:1 based on propensity score. There was no difference in vasopressor support requirements (49.4% vs 54%; P= .65) or in those experiencing a greater than 20% decrease in mean arterial pressure from baseline (58.6% vs 63.2%; P= .53) in the CIV propofol and non-CIV propofol groups. Furthermore, there were no differences in any secondary outcomes including hospital mortality (32.2% vs 33.3%; P= .87). CONCLUSIONS: Continuous intravenous propofol for sedation did not increase vasopressor requirements in this septic population. Furthermore, CIV propofol was not associated with significant differences in the use of multiple vasopressors, change in mean arterial pressure, length of stay, or mortality.

Antithrombotic Usage Patterns in the Era of New Oral Anticoagulant Options for Atrial Fibrillation.

BACKGROUND: Appropriate treatment reduces the risk of stroke in patients with atrial fibrillation (AF). Despite the known benefits of warfarin, anticoagulation prescribing rates remain inadequate in high-risk patients. Over the last 6 years, 4 novel oral anticoagulants have been approved for use for stroke prophylaxis in non-valvular AF (NVAF), which may allow prescribers to tailor therapy for each NVAF patient. OBJECTIVE: The goal of this investigation was to determine the effect of dabigatran and rivaroxaban availability on the rate of anticoagulant prescribing at hospital discharge in patients with a principal diagnosis of NVAF. METHODS: A retrospective chart review of adult patients presenting with NVAF (CHADS2 score ≥2) was conducted using a historical control group of patients from 2009 compared to patients admitted in 2012 following formulary availability of dabigatran and rivaroxaban. In addition to antithrombotic therapy prescribed, subsequent hospitalizations during a 1-year period were reviewed for major bleeding and stroke events. RESULTS: Two hundred patients were enrolled in the study. The rate of anticoagulant prescribing in the 2009 and 2012 groups was 68.3% and 77.1%, respectively (p = .16). Of the patients in the 2012 group prescribed an anticoagulant, 58 (64%) received warfarin, 26 (28%) received dabigatran, and 7 (8%) received rivaroxaban. One patient (1.2%) in the 2009 group and 4 patients (4.4%) in the 2012 group had a major bleed (p = .4). CONCLUSION: There was no statistical difference in the rate of anticoagulant prescribing between the 2 groups. Despite the availability of additional anticoagulant options, the rate of prescribing remains suboptimal in this high-risk population.

Consequences of treating false positive heparin-induced thrombocytopenia.

Identification of patients with heparin-induced thrombocytopenia is encumbered by false positive enzyme-linked immuno assay (ELISA) antibody results, therefore a serotonin release assay (SRA) is used for confirmation. Recently, several studies have demonstrated that increasing the optical density (OD) threshold (currently at 0.4) of the antibody test enhances the positive predictive value. The purpose of this study was to determine the frequency of patients who were ELISA antibody positive but SRA negative, and the costs and bleeding events associated with alternative anticoagulant treatment. We hypothesized that treating patients with a positive ELISA antibody OD value of <1.0 would result in increased cost and bleeding risk. This retrospective chart review was conducted on adult hospitalized patients from 2011 to 2013. Patients with positive ELISA antibodies (OD of 0.4-1.0) and an SRA result were included. Eighty-five patients were identified with positive antibodies (average OD of 0.66), 100 % of which were found to be SRA negative. A total of 59 patients (69 %) received alternative anticoagulants. The average duration of treatment was 3.1 days, and 4 patients (4.7 %) experienced a bleeding event. The cost of testing and laboratory monitoring was $36,346 and the cost of the alternative anticoagulants totaled $47,179. The total cost was $83,525, with an average total cost per patient of $982. This study adds to the body of literature suggesting treatment should only be initiated if the OD is one or greater. The high false positive rate caused increased cost and some bleeding events.

Assessing the Quality of Database Search Strategies Utilized by Meta-analyses That Evaluate Infectious Disease Drug Therapy.

Meta-analyses are increasingly influencing clinical practice, but significant methodological flaws have been reported. The purpose of this study was to evaluate the quality of search strategies utilized by anti-infective meta-analyses. The Embase database was searched for meta-analyses evaluating anti-infective drug therapy; 103 of 268 identified citations met inclusion criteria and were evaluated. A total of 80.6% of meta-analyses used search terms, and an average of 4.3 databases (Medline, 98.1%; Cochrane, 93.2%; Embase, 76.7%) were searched to identify relevant articles for inclusion. The majority of meta-analyses used a quality assessment tool (84.5%) and reported positive results (59.2%). The average impact factor of journals publishing meta-analyses was 5.7 ± 3.4. The number of resources searched was associated with the impact factor ( P = .0013). The majority of anti-infective meta-analyses used rigorous search strategies to identify all relevant studies for evaluation. This finding is inconsistent with reports in other therapeutic areas that have questioned the quality of meta-analyses, and it may increase confidence in anti-infective meta-analyses.

Post-translational glycosylation of target proteins implicate molecular mimicry in the pathogenesis of HTLV-1 associated neurological disease.

We hypothesized that molecular mimics between human T lymphotropic virus type 1 (HTLV-1) and human autoantigens were based upon post-translational modification of target proteins. Proteins purified from MT-2 (HTLV-1 infected) and Jurkat (HTLV-1 negative) cells were used for western blotting with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) IgG. In contrast to normal IgG, HAM/TSP IgG immunoreacted with proteins in MT-2 cells at 22-24 kDa, pI 8.0, which were identified as peroxiredoxin 1 and HTLV-1-p24-(gag) by mass spectroscopy. Western blots following glycoprotein purification showed that HAM/TSP IgG reacted with PrX-1 and p24 in MT-2 cells but not in Jurkat cells, indicating that the mimicking target proteins were glycosylated. These data suggest that post-translational glycosylation of target proteins may play a role in the pathogenesis of HAM/TSP.

Strain differences in allele and expression levels of CD72 on B-lymphocytes from NOD, AKR, NON and C57BL/6 mice.

The B-lymphocyte marker CD72 has multiple alleles and serves crucial and nonredundant roles in B-cell development and activation. B-lymphocytes play an important role in development of autoimmune diabetes in NOD mice, therefore we examined the patterns of expression of CD72 and its alloantigens on splenic lymphocytes from 4-week-old NOD/LtJ mice. Comparisons of CD72 expression were made between NOD mice and three non-diabetic strains, NON/LtJ mice, C57BL/6J and AKR/J. Use of allele-specific monoclonal antibodies revealed that the previously uncharacterized NON strain expresses either the a or d allele, whereas NOD and AKR mice were confirmed to express the rare c allele. Flow cytometric analysis revealed differential expression between the strains. Whereas NON, C57BL/6 and AKR mice expressed CD72 on 98, 94 and 92% of their B-lymphocytes (CD19+ cells), the NOD mice only expressed this regulatory marker on 78% of their B-lymphocytes. Furthermore, CD72 expression levels on CD72 positive cells were lower in NOD mice than in other three non-diabetic strains. The presence of the CD72c allele, as well as its low level of expression in NOD mice at 4 weeks of age, may be associated with B-lymphocyte hyper-responsiveness and resistance to activation-induced cell death.