Kiranpal Sangha

Recommendations for the Critical Care Management of Devastating Brain Injury: Prognostication, Psychosocial, and Ethical Management

Devastating brain injuries (DBIs) profoundly damage cerebral function and frequently cause death. DBI survivors admitted to critical care will suffer both intracranial and extracranial effects from their brain injury. The indicators of quality care in DBI are not completely defined, and despite best efforts many patients will not survive, although others may have better outcomes than originally anticipated. Inaccuracies in prognostication can result in premature termination of life support, thereby biasing outcomes research and creating a self-fulfilling cycle where the predicted course is almost invariably dismal. Because of the potential complexities and controversies involved in the management of devastating brain injury, the Neurocritical Care Society organized a panel of expert clinicians from neurocritical care, neuroanesthesia, neurology, neurosurgery, emergency medicine, nursing, and pharmacy to develop an evidence-based guideline with practice recommendations. The panel intends for this guideline to be used by critical care physicians, neurologists, emergency physicians, and other health professionals, with specific emphasis on management during the first 72-h post-injury. Following an extensive literature review, the panel used the GRADE methodology to evaluate the robustness of the data. They made actionable recommendations based on the quality of evidence, as well as on considerations of risk: benefit ratios, cost, and user preference. The panel generated recommendations regarding prognostication, psychosocial issues, and ethical considerations.

Recommendations for the critical care management of devastating brain injury: prognostication, psychosocial, and ethical management : a position statement for healthcare professionals from the neurocritical care society

Devastating brain injuries (DBIs) profoundly damage cerebral function and frequently cause death. DBI survivors admitted to critical care will suffer both intracranial and extracranial effects from their brain injury. The indicators of quality care in DBI are not completely defined, and despite best efforts many patients will not survive, although others may have better outcomes than originally anticipated. Inaccuracies in prognostication can result in premature termination of life support, thereby biasing outcomes research and creating a self-fulfilling cycle where the predicted course is almost invariably dismal. Because of the potential complexities and controversies involved in the management of devastating brain injury, the Neurocritical Care Society organized a panel of expert clinicians from neurocritical care, neuroanesthesia, neurology, neurosurgery, emergency medicine, nursing, and pharmacy to develop an evidence-based guideline with practice recommendations. The panel intends for this guideline to be used by critical care physicians, neurologists, emergency physicians, and other health professionals, with specific emphasis on management during the first 72-h post-injury. Following an extensive literature review, the panel used the GRADE methodology to evaluate the robustness of the data. They made actionable recommendations based on the quality of evidence, as well as on considerations of risk: benefit ratios, cost, and user preference. The panel generated recommendations regarding prognostication, psychosocial issues, and ethical considerations.

Pharmacokinetic Optimisation of the Treatment of Embolic Disorders

SummaryManagement of thromboembolic disease involves administration of anticoagulants, thrombolytics or antiplatelet agents to lyse or prevent thrombus extension. Despite widespread use and decades of experience with some of these agents, much is unknown about the effects of dose and plasma concentration on patient response.Unfractionated heparin (UFH) improves outcome in many thromboembolic disorders when administered to a target activated partial thromboplastin time (aPTT) or plasma heparin concentration. UFH exhibits dose-dependency both with absorption from subcutaneous sites and elimination. Doses based on bodyweight or estimated blood volume attain therapeutic aPTTs faster than fixed or standard doses. Low molecular weight heparins (LMWHs) were developed to increase the anti-factor Xa: anti-factor IIa activities. Several different LMWHs are as effective as UFH in treating deep venous thrombosis. Evidence fails to support a relationship between anti-factor Xa activity and either thrombosis evolution or bleeding. No comparisons have been made between bodyweight-based and anti-factor Xa activity-based doses.The dose of orally administered warfarin is adjusted to achieve a target International Normalised Ratio (INR). Maintenance doses are estimated on the basis of the patient’s INR during the first 3 days of therapy: the dose required to achieve an optimal INR decreases with age >50 years.The thrombolytic agents are administered in standard doses to achieve rapid thrombolysis with minimal alteration in systemic haemostasis. Accelerated intravenous alteplase may result in the highest rate of coronary artery reperfusion. Nevertheless, standard doses of streptokinase, anisoylated plasminogen streptokinase complex and alteplase result in similar 1-month mortality rates. The minimal advantage seen with alteplase is offset by higher rates of stroke. Future trials will focus on administration strategies achieving rapid thrombolysis, while minimising the risk of serious bleeding.With the antiplatelet agents, unpredictability in the pharmacokinetic parameters of different products has confounded interpretation of published reports. Optimal aspirin (acetylsalicylic acid) administration would include administration of an initial dose of 160 to 325mg after an acute vascular event, followed by maintenance dosages of approximately 75 mg/day for prophylaxis or treatment. Ticlopidine does not exhibit a relationship between either plasma concentration or dose and adverse effects, while pharmacodynamic effects may be dose-, but not plasma concentration-, dependent. The correlation between the concentration of dipyridamole and some of its antiplatelet effects may be the strongest amongst all the antiplatelet agents. However, unfortunately all clinical trials used standard doses and the current consensus is that dipyridamole alone is not an effective antiplatelet agent.

Pharmacokinetics of Once-Dally Dosing of Gentamicin in Surgical Intensive Care Unitpatients with Openfractures

Objective: To compare the first-dose pharmacokinetic parameters of gentamicin 6 mg/kg and 2 mg/kg in stable, nonobese surgical intensive care unit patients with open extremity fractures receiving gentamicin prophylactically. Methods: Serial blood samples were obtained over 8 or 24 hours following the first dose of gentamicin. Serum concentrations of gentamicin were measured using fluorescence polarization immunoassay and analyzed by noncompartmental means. Results: Eleven patients were enrolled, 7 in the 6 mg/kg group and 4 in the 2 mg/kg group. The median (6 vs. 2 mg/kg) age was 29 versus 28 years; serum creatinine 80 versus 88 μmol/L; and APACHE H score 13 versus 10. The mean ± SD (μg/mL) of concentration at the end of the 30-minute infusion (Cmax), concentration 30 minutes after the end of the infusion (Cpk), and concentration at the end of the dosing interval for 6 versus 2 mg/kg were: 35.0 ± 19.0 versus 10.1 ± 1.77; 17.0 ± 2.7 versus 5.4 ± 0.4, and 0.45 ± 0.31 versus 0.69 ± 0.11, respectively. Area under the curves0-∞ (AUC0-∞), apparent volume of distribution, and half-life were: 89.0 ± 28.9 versus 26.1 ± 1.2 mg·h/L, 0.40 ± 0.10 versus 0.47 ± 0.14 L/kg, and 4.0 ± 1.1 versus 4.3 ± 1.5 h, respectively. Conclusions: The first-dose pharmacokinetics of gentamicin 6 mg/kg resulted in a proportional rise in Cmax, Cpk, and AUC0-∞, compared with gentamicin 2 mg/kg in patients with open fractures, but with greater variability.

Response to "Characterization of unbound phenytoin concentrations in neurointensive care unit patients using a revised Winter-Tozer equation" by Sean P. Kane, Adam P. Bress, and Eljim P. Tesoro.

TO THE EDITOR: We read with great interest the study by Kane et al evaluating multiple equations to correct total phenytoin levels in neurointensive care patients. This study is to be commended for its large sample size and focus on critically ill patients, who have multiple reasons for altered phenytoin concentrations. They found the traditional Winter-Tozer (WT) equation significantly underpredicted patients’ actual free phenytoin concentrations and concluded it is not appropriate to use in this population. They found greater correlation between predicted and actual free phenytoin concentrations with a modified WT equation and an equation developed through multivariate analysis. Previous studies evaluating the WT equation’s predictive ability have shown mixed results. We conducted an analysis of internal data in our neurointensive patient population to see how patient’s phenytoin binding changes throughout their stay. Our cohort included 100 patients and 556 paired total and free phenytoin concentrations. The average free fraction of phenytoin in our group was 18.8% and the average albumin was 2.7 g/dL. Following the results from Kane et al, we applied the 3 equations used (WT, multivariate liner regression model, and modified WT coefficient) to our data in an attempt to validate their results. We applied these equations to each patient’s first phenytoin concentrations and albumin level as Kane et al did (group 1, n = 92), then to the patient’s phenytoin concentrations and albumin levels throughout their entire intensive care unit stay (group 2, n = 312). Surprisingly, we found the traditional WT equation had the greatest correlation when compared with the other 2 equations, and overall, all 3 equations correlated poorly with actual free phenytoin concentrations (see Table 1). These markedly different results may be because of differences in study design and baseline demographics. Our data are from the patients’ entire stay in the neurointensive care unit (each patient had multiple phenytoin concentrations) versus within the first 24 hours of admission as Kane et al used. Also, our patients had a mean albumin of 2.7 g/ dL versus a mean albumin of 3.3 g/dL in Kane et al’s group. Overall, we agree with Kane et al’s idea of developing new predictive equations accounting for other variables in addition to albumin. Both our results have shown that the WT equation is not reliable in neurointensive patients. Future studies evaluating predictive phenytoin equations should include a variety of variables in their analysis.

Recommendations for the Critical Care Management of Devastating Brain Injury

Devastating brain injuries (DBIs) profoundly damage cerebral function and frequently cause death. DBI survivors admitted to critical care will suffer both intracranial and extracranial effects from their brain injury. The indicators of quality care in DBI are not completely defined, and despite best efforts many patients will not survive, although others may have better outcomes than originally anticipated. Inaccuracies in prognostication can result in premature termination of life support, thereby biasing outcomes research and creating a self-fulfilling cycle where the predicted course is almost invariably dismal. Because of the potential complexities and controversies involved in the management of devastating brain injury, the Neurocritical Care Society organized a panel of expert clinicians from neurocritical care, neuroanesthesia, neurology, neurosurgery, emergency medicine, nursing, and pharmacy to develop an evidence-based guideline with practice recommendations. The panel intends for this guideline to be used by critical care physicians, neurologists, emergency physicians, and other health professionals, with specific emphasis on management during the first 72-h post-injury. Following an extensive literature review, the panel used the GRADE methodology to evaluate the robustness of the data. They made actionable recommendations based on the quality of evidence, as well as on considerations of risk: benefit ratios, cost, and user preference. The panel generated recommendations regarding prognostication, psychosocial issues, and ethical considerations.

581: CLINICAL IMPACT OF HYPERCHLOREMIA SECONDARY TO HYPERTONIC SODIUM CHLORIDE ADMINISTRATION

Learning Objectives: Itravenous (IV) hypertonic sodium chloride (HTS) has multiple clinical indications. Isotonic sodium chloride and subsequent hyperchloremia have been associated with acute kidney injury (AKI), prolonged hospital length of stay (LOS), and increased mortality. These associations have not been evaluated with HTS use. The primary objective of this study is to compare the incidence of AKI among peak serum chloride concentrations in patients receiving HTS. Methods: This single-center, retrospective, observational study analyzed adult patients admitted >72 hr and reveiving ≥15 grams of sodium chloride via IV HTS. Patients were divided into tertiles based on peak serum chloride: tertile 1 (T1) ≤108 mmol/L; tertile 2 (T2) 109–116 mmol/L; tertile 3 (T3) ≥117 mmol/L. AKI and in-hospital mortality rates were compared among tertiles. Multivariate logistic regression was performed to identify factors associated with AKI development or mortality. Results: 136 patients were included (T1, 43 [32%]; T2, 52 [38%]; T3, 41 [30%]). Baseline characteristics were similar among tertiles with the exception of T1 including fewer traumatic admissions (19 v 52 v 42%;p=0.003) and more hyponatremia diagnoses (14 v 4 v 0%;p=0.018). Increase in serum chloride from baseline was different among tertiles (6 v 9 v 16%;p<0.001). Rate of AKI increased with peak serum chloride (2 v 10 v 22%;p=0.015). Multivariate logistic regression identified that peak serum chloride independently predicted AKI development (OR 7.1, 95% CI 1–50;p=0.049). Hospital (13 v 16 v 13;p=0.053) and ICU (8 v 11 v 11;p=0.124) LOS (days) were similar among groups. Mortality rate increased with peak serum chloride (5 v 14 v 32%;p=0.003). No factors were identified as independent predictors of mortality. Conclusions: After adjusting for concurrent nephrotoxins and other confounding variables, increasing magnitude of serum chloride was associated with AKI among patients who received HTS. Prospective, multicenter studies are needed to confirm this relationship.

Authors' Reply: We Thank the Authors for Taking an Interest in Our Recently Published Research Report.1:

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