The morbidity and outcome of patients with Guillain-Barré syndrome admitted to the intensive care unit

One third of patients with Guillain-Barré syndrome (GBS) require admission to the intensive care unit (ICU), associated with significant risk of morbidity, mortality, and incomplete recovery. METHODS: 76 adult patients with GBS admitted to the ICU at a regional referral center over a 20-year period were studied. We determined the frequency, nature, and predictors of complications they experienced while in the ICU; this morbidity was related to long-term functional recovery and time to regain independent ambulation, extracted from longitudinal follow-up data. RESULTS: ICU stay was a median 21 days and mechanical ventilation (MV) was required in 78% (median duration 28 days). Two-thirds suffered at least one major complication, most commonly pneumonia (54%). Morbidity was strongly associated with MV and male sex. Mortality occurred in only 5 patients (6.5%). Over an average 3 years follow-up, recovery of independent ambulation was seen in 75%, with advanced age being the most powerful predictor of poor outcome. Prolonged MV and severe axonal loss did not preclude a favorable recovery. Time to ambulate was a median 198 days, although recovery could occur as late as ten years after onset; slower recovery was associated with ICU complications, prolonged MV, and early axonal abnormalities. CONCLUSION: Although patients with GBS suffer significant morbidity during protracted ICU stays, with meticulous supportive care, many make gratifying functional recoveries. In severely afflicted patients, this may only be appreciated after extended follow-up.     

Variation in Osmotic Response to Sustained Mannitol Administration

Background  Osmotic agents such as mannitol remain a mainstay in the management of cerebral edema and raised intracranial pressure. Some patients do not respond to sustained mannitol administration with the expected rise in serum osmolality, and this may correlate with lack of therapeutic efficacy. Objective  To examine the variation in osmotic response to mannitol therapy and identify factors associated with a lack of an osmotic response to sustained mannitol administration. Methods  Data on consecutive patients admitted to a Neurology/Neurosurgery Intensive Care Unit who received scheduled doses of mannitol for at least 48 h were extracted from a prospectively collected database. All patients received intravenous isotonic saline solutions and had serial measurements of serum sodium and osmolality, at least twice daily. Non-responders were defined using two thresholds, a rise in serum sodium of ≤1 or ≤5 mEq/l over the 48-hour period. Results  The cohort included 167 patients the majority with intracerebral and subarachnoid hemorrhage and brain tumors. 73 patients (44%) did not respond to mannitol with a rise in sodium of ≥5 mEq/l, and 37 (22%) did not see a rise of 1 mEq/l over 48 h of treatment. There were minor differences between responders and non-responders (≥5 mEq/l) in terms of age (56 ± 15 vs. 48 ± 14), total mannitol dose (0.9 ± 0.2 vs. 0.7 ± 0.2 g/kg), and cumulative fluid balance at 72 h (91 ± 1653 vs. −610 ± 1692 ml). Multivariate analysis found that younger age, lower weight-adjusted mannitol dose, and more negative fluid balance were associated with lack of osmotic response. Discussion  A substantial proportion of patients receiving sustained mannitol do not manifest the expected osmotic response. This lack of response may correlate with the failure of clinical efficacy seen in a subgroup of patients, who then require alternate agents such as hypertonic saline. This association merits further exploration.     

JNK1 but not JNK2 promotes the development of steatohepatitis in mice

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and varying degrees of necroinflammation. Although chronic oxidative stress, inflammatory cytokines, and insulin resistance have been implicated in the pathogenesis of NAFLD, the mechanisms that underlie the initiation and progression of this disease remain unknown. c-Jun N-terminal kinase (JNK) is activated by oxidants and cytokines and regulates hepatocellular injury and insulin resistance, suggesting that this kinase may mediate the development of steatohepatitis. The presence and function of JNK activation were therefore examined in the murine methionine- and choline-deficient (MCD) diet model of steatohepatitis. Activation of hepatic JNK, c-Jun, and AP-1 signaling occurred in parallel with the development of steatohepatitis in MCD diet-fed mice. Investigations in jnk1 and jnk2 knockout mice demonstrated that jnk1, but not jnk2, was critical for MCD diet-induced JNK activation. JNK promoted the development of steatohepatitis as MCD diet-fed jnk1 null mice had significantly reduced levels of hepatic triglyceride accumulation, inflammation, lipid peroxidation, liver injury, and apoptosis compared with wild-type and jnk2 -/- mice. Ablation of jnk1 led to an increase in serum adiponectin but had no effect on serum levels of tumor necrosis factor-alpha. In conclusion, JNK1 is responsible for JNK activation that promotes the development of steatohepatitis in the MCD diet model. These findings also provide additional support for the critical mechanistic involvement of JNK1 overactivation in conditions associated with insulin resistance and the metabolic syndrome.     

Acute cigarette smoke exposure reduces clot lysis -- association between altered fibrin architecture and the response to t-PA

Background

Enhanced thrombolysis is a proposed mechanism for reduced mortality in cigarette smokers with STEMI (“smoker's paradox”). The mechanisms remain unclear but studies suggest fibrin architecture (FA) may affect thrombolysis. Our group has previously shown that acute cigarette smoke exposure (CSE) alters FA. This study was done to evaluate the association between FA, thrombolysis and CSE.

Methods and Results

Otherwise healthy smokers (n = 22) were studied before and after smoking two cigarettes. Non-smokers (n = 22) served as controls. Two ex-vivo models were used to evaluate clot lysis of venous blood and these data were compared to FA as determined by SEM. In the first model, clot lysis in a glass tube at 60 minutes after addition of t-PA was measured. The second model quantified lysis utilizing thromboelastography. With the latter, after a clot reached maximum strength, t-PA was added and clot lysis at 60 min was noted. SEM studies were performed on platelet poor plasma mixed with thrombin and FA was examined at 20 K.Clot lysis was similar in both groups except that post-smoking, TEG showed a significantly lower lysis compared to pre- and non-smoking clots. SEM analysis showed significantly thinner fibers and denser clots post-smoking.

Conclusions

Venous clots from smokers failed to show an enhanced lysis when exposed to t-PA. In fact, acute CSE was associated with changes in FA and increased resistance to thrombolysis. These findings in part may explain enhanced thrombogenicity but suggest that mechanisms other than enhanced fibrinolysis are likely to be responsible for “smoker's paradox.”     

Comparison of self-reported benzodiazepine use and urinalysis among consecutive treatment seekers at a tertiary care drug dependence treatment centre

Information provided by drug dependent patients might be incomplete and/or discrepant. Benzodiazepines are frequently abused, but not necessarily reported, even bythe treatment seeking population. The study aims to compare the self reported benzodiazepine use with a quick and effective urinalysis method. A total of 51 consecutive adult patients were included after an informed consent during their first visit to a tertiary care drug dependence treatment centre. The socio-demographic and clinical details were recorded on a semi-structured proforma. Patients were specifically asked for ever, current and recent benzodiazepine use and thereafter ten ml urine sample was collected to perform urinalysis with cassette test for benzodiazepines. The sample, predominantly males, had a mean age of 37.86 +/-10.46 years. The common primary drugs of use were heroin (52.9%), alcohol (23.5%) and other opioids (21.6%). Drug use was uninterrupted in most of users (72.5%) and ranged from one to forty years. The recent benzodiazepine use was reported by 21.6% of all users whereas urinalysis by cassette test was positive in 50.9% of the treatment seekers. Denial among users was 69.2% and denial among negative self report was 45%. A poor level of agreement (K) was found between results of self-report and urinalysis for all the treatment seekers. Self report of benzodiazepine use is highly questionable among treatment seekers. The urinalysis with cassette test is a quick objective method which is recommended for routine screening.