The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review.

STUDY OBJECTIVE: We synthesize the available evidence on the effect of ketamine on intracranial and cerebral perfusion pressures, neurologic outcomes, ICU length of stay, and mortality. METHODS: We developed a systematic search strategy and applied it to 6 electronic reference databases. We completed a gray literature search and searched medical journals as well as the bibliographies of relevant articles. We included randomized and nonrandomized prospective studies that compared the effect of ketamine with another intravenous sedative in intubated patients and reported at least 1 outcome of interest. Two authors independently performed title, abstract, and full-text reviews, and abstracted data from all studies, using standardized forms. Data from randomized controlled trials and prospective studies were synthesized in a qualitative manner because the study designs, patient populations, reported outcomes, and follow-up periods were heterogeneous. We used the Jadad score and Cochrane Risk of Bias tool to assess study quality. RESULTS: We retrieved 4,896 titles, of which 10 studies met our inclusion criteria, reporting data on 953 patients. One study was deemed at low risk of bias in all quality assessment domains. All others were at high risk in at least 1 domain. Two of 8 studies reported small reductions in intracranial pressure within 10 minutes of ketamine administration, and 2 studies reported an increase. None of the studies reported significant differences in cerebral perfusion pressure, neurologic outcomes, ICU length of stay, or mortality. CONCLUSION: According to the available literature, the use of ketamine in critically ill patients does not appear to adversely affect patient outcomes.

Prophylactic anticoagulation to prevent venous thromboembolism in traumatic intracranial hemorrhage: a decision analysis.

INTRODUCTION: Patients with intracranial hemorrhage due to traumatic brain injury are at high risk of developing venous thromboembolism including deep vein thrombosis (DVT) and pulmonary embolism (PE). Thus, there is a trade-off between the risks of progression of intracranial hemorrhage (ICH) versus reduction of DVT/PE with the use of prophylactic anticoagulation. Using decision analysis modeling techniques, we developed a model for examining this trade-off for trauma patients with documented ICH. METHODS: The decision node involved the choice to administer or to withhold low molecular weight heparin (LMWH) anticoagulation prophylaxis at 24 hours. Advantages of withholding therapy were decreased risk of ICH progression (death, disabling neurologic deficit, non-disabling neurologic deficit), and decreased risk of systemic bleeding complications (death, massive bleed). The associated disadvantage was greater risk of developing DVT/PE or death. Probabilities for each outcome were derived from natural history studies and randomized controlled trials when available. Utilities were obtained from accepted databases and previous studies. RESULTS: The expected value associated with withholding anticoagulation prophylaxis was similar (0.90) to that associated with the LMWH strategy (0.89). Only two threshold values were encountered in one-way sensitivity analyses. If the effectiveness of LMWH at preventing DVT exceeded 80% (range from literature 33% to 82%) our model favoured this therapy. Similarly, our model favoured use of LMWH if this therapy increased the risk of ICH progression by no more than 5% above the baseline risk. CONCLUSIONS: Our model showed no clear advantage to providing or withholding anticoagulant prophylaxis for DVT/PE prevention at 24 hours after traumatic brain injury associated with ICH. Therefore randomized controlled trials are justifiable and needed to guide clinicians.

Canonical WNT/beta-catenin signaling is required for ureteric branching.

WNT/beta-catenin signaling has an established role in nephron formation during kidney development. Yet, the role of beta-catenin during ureteric morphogenesis in vivo is undefined. We generated a murine genetic model of beta-catenin deficiency targeted to the ureteric bud cell lineage. Newborn mutant mice demonstrated bilateral renal aplasia or renal dysplasia. Analysis of the embryologic events leading to this phenotype revealed that abnormal ureteric branching at E12.5 precedes histologic abnormalities at E13.5. Microarray analysis of E12.5 kidney tissue identified decreased Emx2 and Lim1 expression among a small subset of renal patterning genes disrupted at the stage of abnormal branching. These alterations are followed by decreased expression of genes downstream of Emx2, including Lim1, Pax2, and the ureteric tip markers, c-ret and Wnt 11. Together, these data demonstrate that beta-catenin performs essential functions during renal branching morphogenesis via control of a hierarchy of genes that control ureteric branching.

Surrogate decision makers' attitudes towards research decision making for critically ill patients.

PURPOSE: To examine the attitudes and preferences of surrogate decision makers (SDMs) regarding their involvement in the consent to research process for ICU patients. METHODS: We presented 136 SDMs of critically ill patients in five ICUs with four hypothetical research scenarios: baseline interventional study of a placebo controlled RCT; study with higher risk of treatment complication; study comparing two accepted treatments; study with shorter enrolment window. For each we asked SDMs if they would want to be involved in the consent to research decision, and to rate the acceptability of their comfort with, and their sense of burden with their involvement. Participants were screened for symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale. RESULTS: For the baseline scenario, most SDMs wished to be involved in research decision making (90 %; 95 % CI 84-95 %); responses varied little across study permutations. The majority considered their involvement to be acceptable (85 %; 95 % CI 77-90 %), whereas, a small minority rated it as being unacceptable (2 %; 95 % CI 1-6 %). Many were comfortable with being involved (50 %; 95 % CI 41-59 %), but the number decreased when risk of harm was higher (34 %; 95 % CI 26-43 %) or enrolment window was shorter (41 %; 95 % CI 33-50 %). A majority (62 %) reported symptoms of anxiety and many (38 %) had symptoms of depression. CONCLUSION: Most of the interviewed SDMs wished to be involved in research decision making for critically ill and incapable loved ones. Variability existed, however, in their desire to be involved when decisions were time-sensitive or perceived risk was greater.