OBJECTIVES:Sarcopenia is associated with a poor prognosis in the ICU. The purpose of this study was to describe a simple sarcopenia index using routinely available renal biomarkers and evaluate its ...association with muscle mass and patient outcomes.
DESIGN:A retrospective cohort study.
SETTING:A tertiary-care medical center.
PATIENTS:High-risk adult ICU patients from October 2008 to December 2010.
INTERVENTIONS:The gold standard for muscle mass was quantified with the paraspinal muscle surface area at the L4 vertebrae in the subset of individuals with an abdominal CT scan. Using Pearson’s correlation coefficient, serum creatinine-to-serum cystatin C ratio was found to be the best performer in the estimation of muscle mass. The relationship between sarcopenia index and hospital and 90-day mortality, and the length of mechanical ventilation was evaluated.
MEASUREMENTS AND MAIN RESULTS:Out of 226 enrolled patients, 123 (54%) were female, and 198 (87%) were white. Median (interquartile range) age, body mass index, and body surface area were 68 (57–77) years, 28 (24–34) kg/m, and 1.9 (1.7–2.2) m, respectively. The mean (± SD) Acute Physiology and Chronic Health Evaluation III was 70 (± 22). ICU, hospital, and 90-day mortality rates were 5%, 12%, and 20%, respectively. The correlation (r) between sarcopenia index and muscle mass was 0.62 and coefficient of determination (r) was 0.27 (p < 0.0001). After adjustment for Acute Physiology and Chronic Health Evaluation III, body surface area, and age, sarcopenia index was independently predictive of both hospital (p = 0.001) and 90-day mortality (p < 0.0001). Among the 131 patients on mechanical ventilator, the duration of mechanical ventilation was significantly lower on those with higher sarcopenia index (–1 d for each 10 unit of sarcopenia index 95% CI, –1.4 to –0.2; p = 0.006).
CONCLUSIONS:The sarcopenia index is a fair measure for muscle mass estimation among ICU patients and can modestly predict hospital and 90-day mortality among patients who do not have acute kidney injury at the time of measurement.
BACKGROUND:The reported incidence of hypotension and bradycardia in patients receiving dexmedetomidine for sedation commonly exceeds 50%. In this study, we describe the incidence of, patient- and ...treatment-specific risk factors for, and clinical significance of dexmedetomidine-associated hemodynamic instability.
METHODS:This retrospective cohort study was conducted in critically ill adults receiving dexmedetomidine for sedation at Mayo Clinic Hospital in Rochester, MN, during a 1-year period. The primary end point was hemodynamic instabilitya composite of hypotension and/or bradycardia, defined as systolic blood pressure <80 mm Hg, diastolic blood pressure <50 mm Hg, or heart rate <50 beats per minute during dexmedetomidine therapy. Cox proportional hazards models were constructed to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk factors of hemodynamic instability.
RESULTS:Hemodynamic instability occurred in 197 of the analyzed 300 patients receiving dexmedetomidine, resulting in a cumulative incidence of 71% at 24 hours via Kaplan-Meier estimation. In addition to dexmedetomidine, univariate analysis identified age, vasopressor use, low baseline arterial blood pressure, and concomitant sedatives as associated with increased risk of hemodynamic instability. Multivariable analysis demonstrated associations between age (HR, 1.23 per 10 years, 95% CI, 1.10–1.38) and low baseline blood pressure (HR, 2.42 at dexmedetomidine initiation, 95% CI, 1.68–3.49) and risk of hemodynamic instability. Variables such as concomitantly administered cardiac medications or sedative therapies and dexmedetomidine infusion rates >0.7 μg/kg/h were not found to be predictors of hemodynamic instability among the analyzed sample.
CONCLUSIONS:Hemodynamic instability commonly occurs in critically ill adults receiving dexmedetomidine, with more than two thirds of this cohort experiencing hypotension and/or bradycardia within 24 hours of initiation. Increasing age and low baseline arterial blood pressure were associated with the development of hemodynamic instability. These findings suggest that clinicians should be aware of the potential risk of hemodynamic instability when using dexmedetomidine in patients with advanced age or low baseline arterial blood pressure.
Serum cystatin C can improve glomerular filtration rate (GFR) estimation over creatinine alone, but whether this translates into clinically relevant improvements in drug dosing is unclear.
This ...prospective cohort study enrolled adults receiving scheduled intravenous vancomycin while hospitalized at the Mayo Clinic in 2012. Vancomycin dosing was based on weight, serum creatinine with the Cockcroft-Gault equation, and clinical judgment. Cystatin C was later assayed from the stored serum used for the creatinine-based dosing. Vancomycin trough prediction models were developed by using factors available at therapy initiation. Residuals from each model were used to predict the proportion of patients who would have achieved the target trough with the model compared with that observed with usual care.
Of 173 patients enrolled, only 35 (20%) had a trough vancomycin level within their target range (10 to 15 mg/L or 15 to 20 mg/L). Cystatin C-inclusive models better predicted vancomycin troughs than models based upon serum creatinine alone, although both were an improvement over usual care. The optimal model used estimated GFR by the Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) creatinine-cystatin C equation (R(2) = 0.580). This model is expected to yield 54% (95% confidence interval 45% to 61%) target trough attainment (P <0.001 compared with the 20% with usual care).
Vancomycin dosing based on standard care with Cockcroft-Gault creatinine clearance yielded poor trough achievement. The developed dosing model with estimated GFR from CKD-EPIcreatinine-cystatin C could yield a 2.5-fold increase in target trough achievement compared with current clinical practice. Although this study is promising, prospective validation of this or similar cystatin C-inclusive dosing models is warranted.
Levetiracetam is a first‐line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of ...levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67‐year‐old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO. His course was complicated by multiorgan dysfunction including acute renal failure requiring CVVH. On hospital day 6, intravenous levetiracetam, at a loading dose of 2000 mg followed by a maintenance dose of 1000 mg every 12 hours, was initiated for new‐onset seizures. The volume of distribution was 0.65 L/kg, and clearance was measured with peak (ranging from 26.5–39.8 μg/ml) and trough (ranging from 13.9–18.2 μg/ml) concentrations. Elimination half‐life ranged from 8.7–10.1 hours. Renal dysfunction reduces levetiracetam clearance, and dosage reductions are recommended to prevent accumulation. Current CVVH dosing recommendations are based on predicted removal without clinical data. The volume of distribution and clearance in this case were similar to those of a normal healthy patient. Based on these results, we recommend considering an initial levetiracetam dose of 1000 mg every 12 hours for patients receiving CVVH, with dosage adjustments based on therapeutic drug monitoring.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Purpose Although benzodiazepines are first-line drugs for alcohol withdrawal syndrome (AWS), rapidly escalating doses may offer little additional benefit and increase complications. The ...purpose of this study was to evaluate dexmedetomidine's impact on benzodiazepine requirements and hemodynamics in AWS. Materials and Methods This retrospective case series evaluated 33 critically ill adults with a primary diagnosis of AWS from 2006 to 2012 at an academic medical center. Results Dexmedetomidine began a median (interquartile range) of 11 (2, 32) hours into intensive care unit admission and was titrated to an infusion rate of 0.7 (0.4, 0.7) μ g kg − 1 h − 1 to achieve the desired depth of sedation. In the 12 hours after dexmedetomidine began, patients experienced a 20-mg reduction in median cumulative benzodiazepine dose used ( P < .001), a 14-mm Hg lower mean arterial pressure ( P = .03), and a 17-beats/min reduction in median heart rate ( P < .001). Four (12%) patients experienced hypotension (systolic blood pressure < 80 mm Hg) during therapy, and there were no cases of bradycardia (heart rate < 40 beats/min). Conclusion Dexmedetomidine decreased benzodiazepine requirements and improved the overall hemodynamic profile of patients with severe AWS. These results provide promising evidence about the potential benefit of dexmedetomidine for AWS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Purpose Neuromuscular blocking agents (NMBAs) are frequently used in patients with acute respiratory distress syndrome (ARDS). The purpose of this survey is to describe providers' knowledge ...and perceived efficacy and safety of NMBAs in patients with ARDS. Materials and Methods Prospective, multicenter survey of medical intensive care unit intensivists, fellows, nurse practitioners (NPs), physician's assistants (PAs), and pharmacists at five tertiary care centers between July 2012 and May 2013. Results A total of 335 surveys were sent to providers with a 47% response rate. Ninety-eight percent of providers correctly identified that NMBAs lack anxiolytic and analgesic properties. The effect of end organ damage on NMBA clearance was less commonly identified by NPs/PAs for both hepatic (P = .0077) and renal (P = .0272) dysfunction compared to physicians. More NP/PAs identified the association of consciousness with the use of NMBAs than physicians (P = .047). Forty two percent of prescribers reported always or frequently using continuous infusion NMBAs in patients with severe ARDS, with 89% initiating NMBAs due to ventilator dyssynchrony. Prescribers perceived continuous NMBAs to be more effective than inhaled prostaglandins (74% vs. 56%) in severe ARDS, but less safe (45% vs. 84%). Train of four was identified by 54% of prescribers as their primary method for titration. Conclusion Providers are knowledgeable about NMBAs, but educational opportunities exist. Perceptions about the efficacy and safety of NMBAs varied amongst prescribers and inconsistencies existed in the prioritization of management strategies for ARDS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To promote early detection of AKI, recently proposed pretest probability models combine sub-Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria with baseline AKI risk. The primary objective ...of this study was to determine sub-KDIGO thresholds that identify patients with septic shock at highest risk for AKI.
This was a retrospective analysis of 390 adult patients admitted to the medical intensive care unit (ICU) of a tertiary, academic medical center with septic shock between January 2008 and December 2010. Hourly urine output was collected from the time of septic shock recognition (hour 0) to hour 96, urine catheter removal, or ICU discharge (whichever occurred first). All available serum creatinine (SCr) measurements were collected until hour 96. The AKI pretest probability model was assessed during the first 12 hours of resuscitation and included the initial episode of oliguria, increase from baseline to peak SCr level, and Acute Physiology and Chronic Health Evaluation (APACHE) III score in a multivariable receiver-operator characteristic (ROC) analysis. The primary outcome was the incidence of stage II or III (stage II+) AKI defined by KDIGO criteria. Secondary outcomes included the need for RRT and 28-day mortality.
Ninety-eight (25%) patients developed stage II+ AKI after septic shock recognition. APACHE III score and increase in SCr level in the first 12 hours were not statistically associated with stage II+ AKI in multivariable ROC analysis. Consecutive oliguria for 3 hours had fair predictive ability for achieving stage II+ AKI criteria (area under ROC curve, 0.73; 95% confidence interval 95% CI, 0.68 to 0.78), and oliguria for 5 hours demonstrated optimal accuracy (82%; 95% CI, 79% to 86%).
Three to 5 hours of consecutive oliguria in patients with septic shock may provide a valuable measure of AKI risk. Further validation to support this finding is needed.
Objective: To evaluate the quality of available evidence of drug class combinations and their association with the development of acute kidney injury (AKI). Data Sources: A search of MEDLINE and ...Embase databases was completed using the following terms: “risk factor AND (acute kidney injury or acute kidney failure) AND (drug or medication).” Study Selection and Data Extraction: Inclusion criteria were the following: English language, full-text availability, and at least 1 drug-combination. Each citation was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. The literature was evaluated using the quality of evidence component of GRADE. No standardized definition of AKI was applied throughout.. Data Synthesis: Out of 2139 total citations, 151 were assessed for full-text review, with 121 citations (6%) meeting inclusion criteria, producing76 unique drug class combinations. Overall, 56 combinations (73.7%) were considered very low quality; 12 (15.8%) were considered low quality. There were 8 (10.5%) of moderate quality, and no combination was considered high quality. 58 (76%) combinations that had a single citation,with a mean of 1.6 citations per drug class combination. The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics was reported in 10 citations, the largest number of citations. Conclusions: Our study demonstrates a lack of well-designed studies addressing drug class combination–associated AKI. The combination of NSAIDs and diuretics with or without additional renin-angiotensin aldosterone agents had the strongest level of evidence. Despite limitations, the information included in this review may result in additional scrutiny about combining certain individual nephrotoxic drugs.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background
Levetiracetam clearance is dependent on renal (major) and hepatic (minor) elimination pathways. In the setting of organ dysfunction, dose reductions are recommended to prevent ...accumulation. Continuous venovenous hemofiltration (CVVH) has been shown to eliminate levetiracetam, but the preferred dosing regimen when a patient is on CVVH and has concomitant acute liver dysfunction is unknown. The objective of this case is to describe levetiracetam dosing and pharmacokinetics in the setting of CVVH and acute liver dysfunction.
Methods
This is a case report of a single patient.
Results
A 59-year-old male was admitted to the intensive care unit for acute onset multiorgan dysfunction associated with a hematologic disorder. His hospital course was complicated by persistent liver dysfunction with a model for end-stage liver disease score of 47 and renal failure which necessitated initiation of CVVH. On hospital day two, the patient developed new-onset focal seizures secondary to metabolic abnormalities that resulted in the initiation of levetiracetam 1000 mg intravenously twice daily. The peak concentration at steady state was 32.2 mcg/mL, and the trough concentration was 16.1 mcg/mL (goal 12–46 mcg/mL). The volume of distribution was 0.65 L/kg, and the elimination half-life was 11.4 h.
Conclusion
Levetiracetam pharmacokinetics observed in this case approximated those seen in a normal healthy patient and a regimen of 1000 mg twice daily achieved serum trough concentrations at the lower limit of the target range. This case indicates that in a patient with acute liver dysfunction on CVVH, 1000 mg twice daily may be considered as an empiric levetiracetam regimen.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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