Jeffrey J. Fletcher

Comparison of accuracy of optic nerve ultrasound for the detection of intracranial hypertension in the setting of acutely fluctuating vs stable intracranial pressure: post-hoc analysis of data from a prospective, blinded single center study

IntroductionOptic nerve sheath diameter (ONSD) measurement with bedside ultrasound has been shown in many studies to accurately detect high intracranial pressure (ICP). The accuracy of point-in-time ONSD measurement in the presence of ongoing fluctuation of ICP between high and normal is not known. Recent laboratory investigation suggests that reversal of optic nerve sheath distension may be impaired following bouts of intracranial hypertension. Our objective was to compare the accuracy of ONSD measurement in the setting of fluctuating versus stable ICP.MethodsThis was a retrospective analysis of data from prospective study comparing ONSD to invasive ICP. Patients with invasive ICP monitors in the ICU underwent ONSD measurement with simultaneous blinded recording of ICP from the invasive monitor. Three measurements were made in each eye. Significant acute ICP fluctuation (SAIF) was defined in two different ways; as the presence of ICP both above and below 20 mmHg within a cluster of six measurements (Definition 1) and as a magnitude of fluctuation >10 mmHg within the cluster (Definition 2). The accuracy of point-in-time ONSD measurements for the detection of concurrent ICP >20 mmHg within clusters fulfilling a specific definition of SAIF was compared to the accuracy of ONSD measurements within clusters not fulfilling the particular definition by comparison of independent receiver operating characteristic (ROC) curves.ResultsA total of 613 concurrent ONSD-ICP measurements in 109 clusters were made in 73 patients. Twenty-three (21%) clusters fulfilled SAIF Definition 1 and 17 (16%) SAIF Definition 2. For Definition 1, the difference in the area under the curve (AUC) of ROC curves for groups with and without fluctuation was 0.10 (P = 0.0001). There was a fall in the specificity from 98% (95% CI 96 to 99%) to 74% (63 to 83%) and in the positive predictive value from 89% (80 to 95%) to 76% (66 to 84%) with fluctuation. For Definition 2, also, there was a significant difference between the AUC of ROC curves of groups with fluctuation-magnitude >10 mmHg and those with fluctuation-magnitude 5 to 10 mmHg (0.06, P = 0.04) as well as <5 mmHg (0.07, P = 0.01).ConclusionsSpecificity and PPV of ONSD for ICP >20 mmHg are substantially decreased in patients demonstrating acute fluctuation of ICP between high and normal. This may be because of delayed reversal of nerve sheath distension.

Comparison of catheter-related large vein thrombosis in centrally inserted versus peripherally inserted central venous lines in the neurological intensive care unit

OBJECTIVE To compare cumulative complication rates of peripherally (PICC) and centrally (CICVC) inserted central venous catheters, including catheter-related large vein thrombosis (CRLVT), central line-associated bloodstream infection (CLABSI), and line insertion-related complications in neurological intensive care patients. METHODS Retrospective cohort study and detailed chart review for 431 consecutive PICCs and 141 CICVCs placed in patients under neurological intensive care from March 2008 through February 2010. Cumulative incidence of CRLVT, CLABSI, and line insertion-related complications were compared between PICC and CICVC groups. Risk factors for CRLVT including mannitol therapy during dwell time, previous history of venous thromboembolism, surgery longer than 1h during dwell time, and line placement in a paretic arm were also compared between groups. RESULTS During the study period, 431 unique PICCs were placed with cumulative incidence of symptomatic thrombosis of 8.4%, CLABSI 2.8%, and line insertion-related complications 0.0%. During the same period, 141 unique CICVCs were placed with cumulative incidence of symptomatic thrombosis of 1.4%, CLABSI 1.4%, and line insertion-related complications 0.7%. There was a statistically significant difference in CRLVT with no difference in CLABSI or line insertion-related complications. CONCLUSIONS In neurological critical care patients, CICVCs appear to have a better risk profile compared to PICCs, with a decreased risk of CRLVT. As use of PICCs in critical care patients increases, a prospective randomized trial comparing PICCs and CICVCs in neurological critical care patients is necessary to assist in choosing the appropriate catheter and to minimize risks of morbidity and mortality associated with central venous access.

Low pulsatility index on transcranial Doppler predicts symptomatic large-vessel vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND Elevated mean cerebral blood flow velocity (mCBFV) on transcranial Doppler predicts vasospasm of the large intracranial arteries after aneurysmal subarachnoid hemorrhage (aSAH). The pulsatility index (PI) is a measure of distal vascular resistance, which may be low when there is compensatory distal vasodilatation following hypoperfusion caused by large-vessel vasospasm. OBJECTIVE To study the predictive value of low PI for symptomatic large-vessel vasospasm (SLVVS) after aSAH. METHODS Medical records of patients admitted with aSAH between January 2007 and April 2009 were reviewed. Transcranial color-coded duplex (TCCD) sonography was performed daily between days 2 and 14. Patients with unexplained acute neurological decline underwent catheter- or computed tomography-angiography. The lowest recorded PI and the highest mCBFV on TCCD were correlated to the occurrence of SLVVS, angiographic vasospasm, and delayed cerebral infraction in multivariate analysis by use of logistic regression. Functional outcome was assessed at first follow-up. RESULTS Eighty-one patients met inclusion criteria. Mean lowest PI was 0.71 + 0.19. Median highest mCBFV was 135 cm/s (interquartile range 99-194 cm/s). SLVVS was seen in 21 of 81 (26%) patients, whereas 27 of 55 (49%) patients with repeat angiography had moderate or severe angiographic vasospasm. Following multivariate analysis, only the lowest PI was an independent predictor of SLVVS (P = .03, odds ratio 0.04, 95% confidence interval 0.001-0.54), whereas only the highest mCBFV was an independent predictor of angiographic vasospasm (P = .02, odds ratio 1.01, 95% confidence interval 1.002-1.02). SLVVS was independently associated with functional outcome at follow-up. CONCLUSION Low PI on TCCD is an independent predictor of SLVVS after aSAH, whereas mCBFV is a better predictor of angiographic vasospasm.

Cost-Effectiveness of Transfers to Centers With Neurological Intensive Care Units After Intracerebral Hemorrhage

Background and Purpose— Our aim was to estimate the cost-effectiveness of transferring patients with intracerebral hemorrhage from centers without specialized neurological intensive care units (neuro-ICUs) to centers with neuro-ICUs. Methods— Decision analytic models were developed for the lifetime horizons. Model inputs were derived from the best available data, informed by a variety of previous cost-effectiveness models of stroke. The effect of neuro-ICU care on functional outcomes was modeled in 3 scenarios. A favorable outcomes scenario was modeled based on the best observational data and compared with moderately favorable and least-favorable outcomes scenarios. Health benefits were measured in quality-adjusted life years (QALYs), and costs were estimated from a societal perspective. Costs were combined with QALYs gained to generate incremental cost-effectiveness ratios. One-way sensitivity analysis and Monte Carlo simulations were performed to test robustness of the model assumptions. Results— Transferring patients to centers with neuro-ICUs yielded an incremental cost-effectiveness ratio for the lifetime horizon of

Incidence of delayed seizures, delayed cerebral ischemia and poor outcome with the use of levetiracetam versus phenytoin after aneurysmal subarachnoid hemorrhage

47 431 per QALY,

Transfer time to a high-volume center for patients with subarachnoid hemorrhage does not affect outcomes.

91 674 per QALY, and

Fulminant chemical ventriculomeningitis following intrathecal liposomal cytarabine administration.

380 358 per QALY for favorable, moderately favorable, and least-favorable scenarios, respectively. Models were robust at a willingness-to-pay threshold of

A Propensity Score Analysis of the Impact of Dexamethasone Use on Delayed Cerebral Ischemia and Poor Functional Outcomes After Subarachnoid Hemorrhage

100 000 per QALY, with 95.5%, 75.0%, and 2.1% of simulations below the threshold for favorable, moderately favorable, and least-favorable scenarios, respectively. Conclusions— Transferring patients with intracerebral hemorrhage to centers with specialized neuro-ICUs is cost-effective if observational estimates of the neuro-ICU–based functional outcome distribution are accurate. If future work confirms these functional outcome distributions, then a strong societal rationale exists to build systems of care designed to transfer intracerebral hemorrhage patients to specialized neuro-ICUs.

Changes in Therapeutic Intensity Level Following Airway Pressure Release Ventilation in Severe Traumatic Brain Injury

Current guidelines recommend against the use of phenytoin following aneurysmal subarachnoid hemorrhage (aSAH) but consider other anticonvulsants, such as levetiracetam, acceptable. Our objective was to evaluate the risk of poor functional outcomes, delayed cerebral ischemia (DCI) and delayed seizures in aSAH patients treated with levetiracetam versus phenytoin. Medical records of patients with aSAH admitted between 2005-2012 receiving anticonvulsant prophylaxis with phenytoin or levetiracetam for >72 hours were reviewed. The primary outcome measure was poor functional outcome, defined as modified Rankin Scale (mRS) score >3 at first recorded follow-up. Secondary outcomes measures included DCI and the incidence of delayed seizures. The association between the use of levetiracetam and phenytoin and the outcomes of interest was studied using logistic regression. Medical records of 564 aSAH patients were reviewed and 259 included in the analysis after application of inclusion/exclusion criteria. Phenytoin was used exclusively in 43 (17%), levetiracetam exclusively in 132 (51%) while 84 (32%) patients were switched from phenytoin to levetiracetam. Six (2%) patients had delayed seizures, 94 (36%) developed DCI and 63 (24%) had mRS score >3 at follow-up. On multivariate analysis, only modified Fisher grade and seizure before anticonvulsant administration were associated with DCI while age, Hunt-Hess grade and presence of intraparenchymal hematoma were associated with mRS score >3. Choice of anticonvulsant was not associated with any of the outcomes of interest. There was no difference in the rate of delayed seizures, DCI or poor functional outcome in patients receiving phenytoin versus levetiracetam after aSAH. The high rate of crossover from phenytoin suggests that levetiracetam may be better tolerated.

A case-cohort study with propensity score matching to evaluate the effects of mannitol on venous thromboembolism.

OBJECTIVES The objective of our study was to examine patients with aneurysmal subarachnoid hemorrhage transferred and directly admitted to our institution in order to determine how transfer time affects outcomes. METHODS A retrospective cohort study was performed of all patients undergoing treatment for aneurysmal subarachnoid hemorrhage between 2005 and 2012 at the University of Michigan. Variables, including transfer time, were tested for their independent association with the primary outcomes of symptomatic vasospasm and 12-month outcome as well as secondary outcomes of aneurysm rebleeding and 12-month mortality. RESULTS During the study period, 263 (87.4%) patients were transferred to our institution and 38 (12.6%) were directly admitted for treatment of aneurysmal subarachnoid hemorrhage. Transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. Higher Hunt-Hess grade was associated with the occurrence of symptomatic vasospasm as well as with poorer 12-month outcome. CONCLUSIONS Transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. We believe our data argue that protocols should emphasize early resuscitation and stabilization followed by safe transfer rather than a hyperacute transfer paradigm. However, transfer time should be minimized as much as possible so as not to delay time to definitive treatment.