Brief review: History, concept and controversies in the neurological determination of death

PURPOSE: Despite general worldwide acceptance of the concept of neurological determination of death (NDD), inconsistencies in clinical criteria and ancillary testing requirements remain. Numerous guidelines for NDD may be applied in clinical practice by a variety of medical practitioners, but the scientific rationale for specific guideline recommendations often remains unclear. This review examines the evolution of NDD, and seeks to provide scientific validation for existing NDD criteria. SOURCE: English language peer-reviewed medical journals and established contemporary medical texts. PRINCIPAL FINDINGS: Currently published guidelines appear to have evolved from the work of the ad hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. The Conference of the Royal Colleges and Faculties of the United Kingdom refined the criteria and subsequently adopted the principal of brainstem death. While the fundamentals of NDD guidelines are remarkably consistent worldwide, specific criteria and requirements are often inconsistent. CONCLUSION: Numerous controversies regarding NDD continue to exist, necessitating further scientific clarification of these issues. More recently published guidelines representing the collective opinion of world experts in NDD based upon best current scientific evidence are available in current medical journals.     

Cervical nerve root stimulation. Part I: technical aspects and normal data.

OBJECTIVE: Cervical nerve root stimulation (CRS) is a technique of assessing the proximal segments of motor axons destined to upper extremity muscles. Few studies report normal values. The objective was to determine CMAP onset-latencies and CMAP amplitude, area, and duration changes in healthy controls for the abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps, and riceps muscles. In addition, to determine the tolerability of CRS, as measured by the visual analog scale (VAS). METHODS: We studied 21 healthy volunteers prospectively with CRS using four target muscles (APB, ADM, biceps, and triceps) bilaterally. Collision studies were used in all APB recordings. VAS was obtained in all subjects. RESULTS: Mean CMAP onset-latencies were: APB 14 +/- 1.5 ms; ADM 14.2 +/- 1.5 ms; biceps 5.4 +/- 0.6 ms; triceps 5.4 +/- 1.0 ms. Onset-latency significantly correlated with height for all nerves. The mean change in CMAP amplitude and area (%) between most distal stimulation and CRS was: APB reduction of 15.1 +/- 11.6 and 4.9 +/- 3.6%; ADM reduction of 21.1 +/- 10.7 and 17.2 +/- 8.8; biceps reduction of 10 +/- 11.5 and reduction of 8.7 +/- 6.8; triceps increase of 3.3 +/- 5.2 and 11.0 +/- 9.9% respectively. Mean CMAP duration change between most distal stimulation and CRS was: APB, increase of 20.4 +/- 7.4%; ADM, increase of 14.4 +/- 8.5%; biceps, increase of 13.9 +/- 10.8%; triceps, increase of 7.7 +/- 6.7%. The mean VAS score was 3.8 +/- 1.2, and all subjects completed the study. CONCLUSIONS: The present study establishes normative data and indicates that CRS is a well-tolerated technique. SIGNIFICANCE: The normal values may be used as reference data for the needle CRS technique in the assessment of proximal conduction abnormalities.     

Sources of Variability in the Detection of Cerebral Emboli with Transcranial Doppler During Cardiac Surgery

OBJECTIVE: The application of intensity thresholds for embolus detection with transcranial Doppler (TCD) can exclude from analysis an unrecognized proportion of high-intensity transient signals (HITS))whose intensities are below the threshold. The lack of consistent threshold criteria between clinical trials may explain part of the discrepancy in the reported HITS counts. We investigated the effect of choosing different thresholds on the sensitivity and specificity of detecting HITS during cardiopulmonary bypass (CPB). METHODS: Two observers independently analyzed TCD recordings from 8 patients under CPB. Doppler signals were classified as true HITS, equivocal HITS, artifacts, and Doppler speckles according to preestablished criteria. The relative intensity of Doppler signals was measured by two different methods (TCD software vs manual). Receiver Operating Characteristic curves determined the optimal threshold for each of the two intensity methods. RESULTS: Reviewers achieved agreement in 96% of 2190 Doppler signals (kappa = 0.90). Relative intensities calculated with the TCD-software method were 3 dB (95% CI: 3.0-3.4) higher than the manual method. The optimal threshold was found at 10 dB (sensitivity: 99%; specificity: 90.8%) with the software method and at 7 dB with the manual method (sensitivity: 96%; specificity: 83%). The use of an intensity threshold 2 dB higher than the optimal increased the rejection of true HITS by 8% and 14%, respectively. CONCLUSIONS: Using intensity thresholds higher than the optimal for embolus detection decreases HITS counts. Choosing a threshold depends on the type of method used for measuring the signal intensity. Uniform threshold criteria and comparative studies between different Doppler devices are necessary for making clinical trials more comparable.     

The development of a laparoscopic donor nephrectomy program in a de novo renal transplant program: Evolution of technique and results in over 200 cases.

BACKGROUND AND OBJECTIVES: In 1999, our institution began a kidney transplant program with collaboration between the departments of General Surgery/Transplantation and Urology. From the onset, donor nephrectomies were performed laparoscopically and are currently the domain of Urology, which had no prior laparoscopic experience before this undertaking. We reviewed our experience. METHODS: A database of our experience was kept prospectively from June 1999 to November 2004. Records of both donors and recipients were reviewed. Special attention was directed toward our changes in technique and their relationship to outcomes, with emphasis on graft extraction and overall complication rates. RESULTS: We reviewed the records of 205 consecutive procedures. We report excellent donor outcomes, including mean operative time (112 minutes), estimated blood loss (120 mL), and length of stay (2.3 days). Complication (14.1%) and open conversion (1.5%) rates were low. For the recipients, early (98.0%) and 1-year (94.7%) graft survival, and ureteral ischemia (2.4%) rates were also appropriate with contemporary experience. CONCLUSIONS: We report our results on laparoscopic donor nephrectomy in a de novo renal transplant program. Because of this experience, we have ventured into other horizons of urologic laparoscopy and currently produce enough volume to support a laparoscopic fellowship. We feel that a productive donor nephrectomy program can enhance urologic laparoscopic programs and should be taken advantage of when available.     

A prospective, randomized clinical trial comparing two hyperbaric treatment protocols for carbon monoxide poisoning.

INTRODUCTION: The optimal hyperbaric oxygen (HBO2) treatment protocol for acute carbon monoxide (CO) poisoning is unknown. This is indicated by one study that found 18 different protocols to treat CO poisoning by North American multiplace hyperbaric facilities. A pilot study was conducted to evaluate the feasibility of randomizing patients to different protocols and to determine whether any large differences in clinical outcome were present between the two most common protocols. METHODS: Adult patients with accidental CO poisoning resulting in transient loss of consciousness, presentation to the emergency department within 12 hours, primary language English, high school education, and residence within 100 miles of the hyperbaric facility were recruited. Enrolled patients were randomized to one HBO2 treatment at 2.4 atmospheres absolute (atm abs) pressure with 90 minutes of 100% oxygen breathing vs. treatment by the US Air Force CO protocol (3.0 atm abs maximum pressure). A neurocognitive screening test was performed immediately after hyperbaric treatment and repeated 14-21 days later. RESULTS: From 1995 to 2002, 30 patients age 21 to 88 years were randomized, 18 to treatment at 2.4 atm abs and 12 to 3.0 atm abs. Average carboxyhemoglobin level for the population was 24.8 +/- 8.8% (mean +/- SD). Delay to hyperbaric treatment averaged 313 +/- 129 minutes. Neither variable was different between treatment groups. Six patients had abnormal neurocognitive testing immediately following hyperbaric treatment, 4 in the 2.4 atm abs group (22%) and 2 in the 3.0 atm abs group (17%) (P=0.71). One patient in each group demonstrated abnormality on delayed testing (p=0.75). One in each group did not return for follow-up. CONCLUSIONS: It is feasible to randomize CO-poisoned patients to different hyperbaric treatment protocols. Determination of differences in efficacy between treatment protocols will require a large multicenter trial with the use of detailed neurocognitive testing.     

166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation.     

Predictors of long-term survival in patients with gallbladder cancer

The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer. A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival <24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status (P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival.