Porphyric neuropathy.

Acute hepatic porphyrias are inherited metabolic disorders that may present with polyneuropathy, which if not diagnosed early can lead to quadriparesis, respiratory weakness, and death. Porphyric neuropathy is an acute to subacute motor predominant axonal neuropathy with a predilection for the upper extremities and usually preceded by a predominantly parasympathetic autonomic neuropathy. The rapid progression and associated dysautonomia mimic Guillain-Barré syndrome but are distinguished by the absence of cerebrospinal fluid albuminocytologic dissociation, progression beyond 4 wk, and associated abdominal pain. Spot urine test to assess the porphyrin precursors delta-aminolevulinic acid and porphobilinogen can provide a timely diagnosis during an acute attack. Timely treatment with intravenous heme, carbohydrate loading, and avoidance of porphyrinogenic medications can prevent further neurological morbidity and mortality.

Serum brain-derived neurotrophic factor (BDNF) concentration predicts polyneuropathy and overall survival in multiple myeloma patients.

Brain-derived neurotrophic factor (BDNF) is a protein with a potent influence on several aspects of neuronal and blood vessel functions. However, its prognostic potential and functional role in multiple myeloma (MM) remain largely unknown. In this study, we investigated the influence of BDNF on the risk of chemotherapy-induced peripheral neuropathy (CIPN) and clinical outcome. Study group consisted of 91 newly-diagnosed MM patients treated with bortezomib and/or thalidomide-based chemotherapy. Detection of BDNF in serum was performed using ELISA. Polyneuropathy was assessed according to the CTCAE Criteria v5. We observed that BDNF concentration correlated with the severity of polyneuropathy (P = 0·0463). Higher BDNF values were noted in patients who responded to treatment (P = 0·0326), and BDNF proved to be a useful marker to predict lack of response after eight cycles of treatment (sensitivity - 100%, specificity - 61·5%, P = 0·0142). Moreover this marker showed significant diagnostic usefulness in diagnosis of CIPN (sensitivity - 76%, specificity - 71·43%; area under the curve (AUC)= 0·77, 95%, confidence interval (CI): 0·64-0·88; P < 0·0001). Low BDNF was an independent, unfavourable prognostic factor associated with reduced overall survival (OS) (hazard ratio (HR) = 2·79, P = 0·0470). In conclusion, BDNF level may play a prognostic role and constitute a useful biomarker in predicting CIPN in MM patients.

Societal costs and burden of hereditary transthyretin amyloidosis polyneuropathy.

Background: Hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN) is a rare life-threatening disease that imposes considerable mortality and morbidity associated with increased costs, high social support and productivity losses. This study aims to estimate the societal costs and burden of ATTRv-PN.Methods: A cost-of-illness (COI) and burden of disease model were specified from a societal perspective, using a prevalence-based approach. Direct and indirect costs were included. Healthcare resource use was retrieved from public databases, previous Portuguese studies and the literature. The burden of disease was expressed in terms of disability-adjusted life years (DALYs), as defined by the World Health Organisation.Results: In 2016, the total annual COI of ATTRv-PN in Portugal was 52,502,796€ and the mean cost per patient was 28,152€ (79% direct; 21% indirect costs). Treatments accounted for 52% of total costs, while 0.18% were devoted to disease prevention. A total of 2056 DALYs were lost, 26% due to disability and 74% due to death.Conclusions: Annual costs and burden of ATTRv-PN were considerable but within the range of other rare diseases. Policies and public interventions to prevent and reduce the burden of disease should be prioritised, since patients experience excess morbidity, mortality and total costs will likely increase in the future.

Benefit in long-term response and mortality of treatment with intravenous immunoglobulin prior to plasmapheresis in peripheral polyneuropathies.

OBJECTIVES: The benefits of plasmapheresis (PA) for neurologic autoimmune diseases have been widely demonstrated. Little is known about the long-term neurologic prognosis and course after PA and immunosuppressive (IS) and/or intravenous immunoglobulin (IVIG) treatment. We aimed to analyse features associated with short-term response and long-term outcome and prognosis (neurologic status and mortality) of peripheral polyneuropathy (PP) and central nervous system acute inflammatory disease (CNSAID) treated with PA. PATIENTS AND METHODS: A descriptive, retrospective single-centre study from January 2005 to December 2012. RESULTS: There were 26 episodes, which included 16 CNSAID and 10 PP cases. First line therapy included PA (n=4), IS drugs (n=15), and IVIG (n=7). Responses were achieved in 80% and 50% of PP and CNSAID cases, respectively. For PP, first line treatment with IVIG and no IS treatment prior to or during PA were variables associated with short-term response (P=0.067), good or stable neurologic status at the end of follow-up (P=0.008), and lower mortality rate (P=0.008). For CNSAID, initial EDSS score≥7 (P=0.019) was related to long-term good or stable neurologic status. During the study period, 177 sessions were conducted; 3.4% had technical complications and 8.5% clinical complications. However, these incidents were all minor and no PA session had to be discontinued. CONCLUSION: The response rates achieved in our patients were similar to those of other research. PA has a safe profile but double-blind, controlled studies are needed to evaluate the synergy of sequential treatment with IGIV followed by PA and the possible benefit for long-term outcome.

Impairments and comorbidities of polyneuropathy revealed by population-based analyses.

OBJECTIVE: To quantify polyneuropathy impairments and comorbidities utilizing the Rochester Epidemiology Project (2010 census = 148,201). METHODS: ICD-9-CM coding identified polyneuropathy cases (2006-2010) and their 5:1 age- and sex-matched controls. Mortality and impairments were evaluated while identifying and adjusting for Charlson Index comorbidities. RESULTS: Overall prevalence of polyneuropathy was 1.66%, and markedly rose to 6.6% in persons older than 60 years. Cases (n = 2,892) had more comorbidities than controls (n = 14,435) with higher median Charlson Index (6 vs 3, p < 0.001). Diabetes with end-organ disease represented the largest increased comorbidity in cases compared with controls (46.8% vs 6.5%). Diabetic polyneuropathy was the most common specific subtype (38.2%). Miscoded idiopathic cases and false-negative controls also commonly had diabetic polyneuropathy. Median modified Rankin Scale score was considerably higher for cases than controls (4 vs 1, p < 0.001). Multiple comorbidities were found associated with polyneuropathy after adjusting for diabetes co-occurrence, including pulmonary disease, dementia, and others. Polyneuropathy was an independent contributor to multiple functional impairments including difficulty walking (odds ratio [OR] = 1.9), climbing stairs (OR = 2.0), using an assistive device (OR = 2.0), fall tendency (OR = 2.4), work disability (OR = 4.2), lower limb amputations (OR = 3.9), and opioid use (OR = 2.7). Prevalent cases had a younger median age at death than controls (80 vs 86 years, p < 0.001), and incident cases had a 6-month shorter survival. CONCLUSIONS: Polyneuropathies have notable neurologic impairments beyond their identified multiple comorbidities. Life expectancy is shortened. Diabetic polyneuropathy is underidentified. The quantified extent of the disease burden and refined comorbidity associations emphasize that greater research efforts and health care initiatives are needed.

[Neurological and psychological long-term effects of sepsis]. / Neurologische und psychische Langzeitfolgen der Sepsis.

BACKGROUND: In addition to the limitations to the health-related quality of life that have been compiled with validated test instruments, a number of former sepsis patients suffer from functional impairments, which are categorized under the terms critical illness polyneuropathy (CIP) or critical illness myopathy (CIM), which have been in existence for over 20 years now. CURRENT FOCUS: The issues of delirium during intensive therapy and persistent residual neurocognitive impairments, posttraumatic stress disorder (PTSD) and states of depression related to perihospital functional development have increasingly attracted notice. FUTURE: The degree of functional deficits resulting from sepsis and the actual quality of life of those affected may, however, be influenced by taking appropriate rehabilitation measures. However, neither therapeutic rehabilitation standards nor any rehabilitation facilities tailored to the needs of these patients currently exist.

Interventions for preventing critical illness polyneuropathy and critical illness myopathy.

BACKGROUND: Critical illness polyneuropathy or myopathy (CIP/CIM) is a frequent complication in the intensive care unit (ICU) and is associated with prolonged mechanical ventilation, longer ICU stay and increased mortality. This is an interim update of a review first published in 2009 (Hermans 2009). It has been updated to October 2011, with further potentially eligible studies from a December 2013 search characterised as awaiting assessment. OBJECTIVES: To systematically review the evidence from RCTs concerning the ability of any intervention to reduce the incidence of CIP or CIM in critically ill individuals. SEARCH METHODS: On 4 October 2011, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, and EMBASE. We checked the bibliographies of identified trials and contacted trial authors and experts in the field. We carried out an additional search of these databases on 6 December 2013 to identify recent studies. SELECTION CRITERIA: All randomised controlled trials (RCTs), examining the effect of any intervention on the incidence of CIP/CIM in people admitted to adult medical or surgical ICUs. The primary outcome was the incidence of CIP/CIM in ICU, based on electrophysiological or clinical examination. Secondary outcomes included duration of mechanical ventilation, duration of ICU stay, death at 30 and 180 days after ICU admission and serious adverse events from the treatment regimens. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and assessed the risk of bias in included studies. MAIN RESULTS: We identified five trials that met our inclusion criteria. Two trials compared intensive insulin therapy (IIT) to conventional insulin therapy (CIT). IIT significantly reduced CIP/CIM in the screened (n = 825; risk ratio (RR) 0.65, 95% confidence interval (CI) 0.55 to 0.77) and total (n = 2748; RR 0.70, 95% CI 0.60 to 0.82) population randomised. IIT reduced duration of mechanical ventilation, ICU stay and 180-day mortality, but not 30-day mortality compared with CIT. Hypoglycaemia increased with IIT but did not cause early deaths.One trial compared corticosteroids with placebo (n = 180). The trial found no effect of treatment on CIP/CIM (RR 1.27, 95% CI 0.77 to 2.08), 180-day mortality, new infections, glycaemia at day seven, or episodes of pneumonia, but did show a reduction of new shock events.In the fourth trial, early physical therapy reduced CIP/CIM in 82/104 evaluable participants in ICU (RR 0.62. 95% CI 0.39 to 0.96). Statistical significance was lost when we performed a full intention-to-treat analysis (RR 0.81, 95% CI 0.60 to 1.08). Duration of mechanical ventilation but not ICU stay was significantly shorter in the intervention group. Hospital mortality was not affected but 30- and 180-day mortality results were not available. No adverse effects were noticed.The last trial found a reduced incidence of CIP/CIM in 52 evaluable participants out of a total of 140 who were randomised to electrical muscle stimulation (EMS) versus no stimulation (RR 0.32, 95% CI 0.10 to 1.01). These data were prone to bias due to imbalances between treatment groups in this subgroup of participants. After we imputed missing data and performed an intention-to-treat analysis, there was still no significant effect (RR 0.94, 95% CI 0.78 to 1.15). The investigators found no effect on duration of mechanical ventilation and noted no difference in ICU mortality, but did not report 30- and 180-day mortality.We updated the searches in December 2013 and identified nine potentially eligible studies that will be assessed for inclusion in the next update of the review. AUTHORS' CONCLUSIONS: There is moderate quality evidence from two large trials that intensive insulin therapy reduces CIP/CIM, and high quality evidence that it reduces duration of mechanical ventilation, ICU stay and 180-day mortality, at the expense of hypoglycaemia. Consequences and prevention of hypoglycaemia need further study. There is moderate quality evidence which suggests no effect of corticosteroids on CIP/CIM and high quality evidence that steroids do not affect secondary outcomes, except for fewer new shock episodes. Moderate quality evidence suggests a potential benefit of early rehabilitation on CIP/CIM which is accompanied by a shorter duration of mechanical ventilation but without an effect on ICU stay. Very low quality evidence suggests no effect of EMS, although data are prone to bias. Strict diagnostic criteria for CIP/CIM are urgently needed for research purposes. Large RCTs need to be conducted to further explore the role of early rehabilitation and EMS and to develop new preventive strategies.

The influence of weaning duration on rehabilitative outcome in early neurological rehabilitation.

BACKGROUND: We investigated if longer weaning is associated with inferior rehabilitative outcome in critical illness polyneuropathy (CIP) and cerebrovascular diseases (CVD). METHODS: We analysed retrospectively weaning protocols and medical histories of 171 tracheotomized patients with CIP and CVD. We assessed weaning durations (WD), independence in activities of daily living, as assessed by the functional independence measure (FIM), mortality rates and discharge modalities in each cohort. Weaning was performed using synchronized intermittent mandatory ventilation (SIMV) with Autoflow® and assisted spontaneous ventilation (ASV). RESULTS: WD was significantly longer in CIP compared to CVD (p < 0.001). Despite shorter in-patient treatment and longer WD, patients with CIP acquired significantly greater gains of improvement than CVD (p = 0.015). Independent living at home was possible in 43% of patients with CIP and in 26% of CVD. Mortality was equal in both groups (13% vs. 6%, p > 0.05). Chronic obstructive pulmonary disease (COPD) showed a trend towards longer weaning durations in both entities (p = 0.06). Higher age significantly correlated with longer WD (p = 0.038, r = 0.16). Longer rehabilitation duration (RD) positively correlated with higher Delta-FIM (DFIM) in both entities (p = 0.006, r = 0.21). CONCLUSION: Longer weaning and its partly negative influence on rehabilitative outcome can be compensated by longer in-patient rehabilitation in CIP and CVD.

Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis.

Critical illness polyneuropathy (CIP) and myopathy (CIM) are complications of critical illness that present with muscle weakness and failure to wean from the ventilator. In addition to prolonging mechanical ventilation and hospitalisation, CIP and CIM increase hospital mortality in patients who are critically ill and cause chronic disability in survivors of critical illness. Structural changes associated with CIP and CIM include axonal nerve degeneration, muscle myosin loss, and muscle necrosis. Functional changes can cause electrical inexcitability of nerves and muscles with reversible muscle weakness. Microvascular changes and cytopathic hypoxia might disrupt energy supply and use. An acquired sodium channelopathy causing reduced muscle membrane and nerve excitability is a possible unifying mechanism underlying CIP and CIM. The diagnosis of CIP, CIM, or combined CIP and CIM relies on clinical, electrophysiological, and muscle biopsy investigations. Control of hyperglycaemia might reduce the severity of these complications of critical illness, and early rehabilitation in the intensive care unit might improve the functional recovery and independence of patients.

Interventions for preventing critical illness polyneuropathy and critical illness myopathy.

BACKGROUND: Critical illness polyneuro-and/or myopathy (CIP/CIM) is an important and frequent complication in the intensive care unit (ICU), causing delayed weaning from mechanical ventilation. It may increase ICU stay and mortality. OBJECTIVES: To examine the ability of any intervention to prevent the occurrence of CIP/CIM. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (October 2007), MEDLINE (January 1950 to April 2008), EMBASE (January 1980 to October 2007), checked bibliographies and contacted trial authors and experts in the field. SELECTION CRITERIA: All randomised controlled trials (RCTs), examining the effect of any intervention on the incidence of CIP/CIM in adult medical or surgical ICU patients. The primary outcome measure was the incidence of CIP/CIM after at least seven days in ICU, based on electrophysiological or clinical examination. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. MAIN RESULTS: Three out of nine identified trials, provided data on our primary outcome measure. Two trials examined the effects of intensive insulin therapy versus conventional insulin therapy. Eight hundred and twenty-five out of 2748 patients randomised, were included in the analysis. The incidence of CIP/CIM was significantly reduced with intensive insulin therapy in the population screened for CIP/CIM (relative risk (RR) 0.65, 95% confidence interval (CI) 0.55 to 0.78) and in the total population randomised (RR 0.60, 95% CI 0.49 to 0.74). Duration of mechanical ventilation, duration of ICU stay and 180-day mortality but not 30-day mortality, were significantly reduced with intensive insulin therapy, in both the total and the screened population. Intensive insulin therapy significantly increased hypoglycaemic events and recurrent hypoglycaemia. Death within 24 hours of the hypoglycaemic event was not different between groups. The third trial examined the effects of corticosteroids versus placebo in 180 patients with prolonged acute respiratory distress syndrome. No significant effect of corticosteroids on CIP/CIM was found (RR 1.09, 95% CI 0.53 to 2.26). No effect on 180-day mortality, new serious infections and glycaemia at day seven was found. A trend towards fewer episodes of pneumonia and reduction of new events of shock was shown. AUTHORS' CONCLUSIONS: Substantial evidence shows that intensive insulin therapy reduces the incidence of CIP/CIM, the duration of mechanical ventilation, duration of ICU stay and 180-day mortality. There was a significant associated increase in hypoglycaemia. Further research needs to identify the clinical impact of this and strategies need to be developed to reduce the risk of hypoglycaemia. Limited evidence shows no significant effect of corticosteroids on the incidence of CIP/CIM, or on any of the other secondary outcome measures, except for a significant reduction of new episodes of shock. Strict diagnostic criteria for the purpose of research should be defined. Other interventions should be investigated in randomised controlled trials.

Acquired weakness, handgrip strength, and mortality in critically ill patients.

RATIONALE: ICU-acquired paresis (ICUAP) is common in survivors of critical illness. There is significant associated morbidity, including prolonged time on the ventilator and longer hospital stay. However, it is unclear whether ICUAP is independently associated with mortality, as sicker patients are more prone and existing studies have not adjusted for this. OBJECTIVES: To test the hypothesis that ICUAP is independently associated with increased mortality. Secondarily, to determine if handgrip dynamometry is a concise measure of global strength and is independently associated with mortality. METHODS: A prospective multicenter cohort study was conducted in intensive care units (ICU) of five academic medical centers. Adults requiring at least 5 days of mechanical ventilation without evidence of preexisting neuromuscular disease were followed until awakening and were then examined for strength. MEASUREMENTS AND MAIN RESULTS: We measured global strength and handgrip dynamometry. The primary outcome was in-hospital mortality and secondary outcomes were hospital and ICU-free days, ICU readmission, and recurrent respiratory failure. Subjects with ICUAP (average MRC score of < 4) had longer hospital stays and required mechanical ventilation longer. Handgrip strength was lower in subjects with ICUAP and had good test performance for diagnosing ICUAP. After adjustment for severity of illness, ICUAP was independently associated with hospital mortality (odds ratio [OR], 7.8; 95% confidence interval [CI], 2.4-25.3; P = 0.001). Separately, handgrip strength was independently associated with hospital mortality (OR, 4.5; 95% CI, 1.5-13.6; P = 0.007). CONCLUSIONS: ICUAP is independently associated with increased hospital mortality. Handgrip strength is also independently associated with poor hospital outcome and may serve as a simple test to identify ICUAP. Clinical trial registered with www.clinicaltrials.gov (NCT00106665).

Treatment of vasculitic peripheral neuropathy: a retrospective analysis of outcome.

BACKGROUND: Vasculitis of the peripheral nervous system (PNS) is rare. There are no controlled treatment trials, and clinical practice is guided by experience from case series and indirectly by analogy with systemic vasculitis. METHODS: We identified patients (n=212) with possible vasculitic peripheral neuropathy (VPN) from the neuropathology and neurophysiology records of two centres over 28 years. Case-notes were available for 181, from which, 106 cases of clinicopathological VPN were identified. Adequate treatment data were available in 100; follow-up data, in 93. RESULTS: Of 106 cases, 95 had systemic vasculitis and 11 had vasculitis confined to the PNS. Pharmacological treatment (94/100 cases) was corticosteroid-based, and included cyclophosphamide in 54; 17 received additional agents. Initial stabilization was achieved in all but six. One-year survival was 90.3%. Of the nine who died in the first years (mean age 73 years), seven had received cyclophosphamide, and all but two had severe, multisystem vasculitis. The neurological relapse rate was 10%. Only one relapse occurred after cyclophosphamide treatment. Outcome was reported as good in 72% (78% in those who relapsed). DISCUSSION: Death and relapse were infrequent in treated patients. Relapse occurred almost exclusively in patients treated with prednisolone alone. Aggressive early treatment with cyclophosphamide may prevent relapse. The current management approach to VPN appears largely effective, especially if cyclophosphamide is used.

High mortality of subjects with endemic ataxic polyneuropathy in Nigeria.

BACKGROUND: Endemic ataxic polyneuropathy, a neurological syndrome that was thought to be benign, has been shown to persist in some communities in south-western Nigeria, where it was first described in the 1950s. OBJECTIVES: This study was conducted to compare mortality of cases and controls, and to determine if mortality is related to exposure to cyanide from cassava foods. MATERIAL AND METHODS: Cases of endemic ataxic polyneuropathy and two groups of controls, one group living in an endemic community and the other group living in a non-endemic community, were followed for 25 months. The outcome was death from medical causes. RESULTS: A total of 5970 subjects, 204 cases and 5766 controls - 4000 controls in the endemic community and 1766 controls in the non-endemic community, were followed. A total of 153 subjects died, 24 cases, 115 controls in the endemic community, and 14 controls in the non-endemic community. Relative risks of death (95% CI), adjusted for age and gender, were 4.5 (2.3-8.9) for cases (P < 0.0001), but 2.6 (1.5-4.6) for controls living in the endemic community (P = 0.001). CONCLUSION: This study shows that endemic ataxic polyneuropathy decreases survival. The finding of lower risk of death in the community with higher exposure to cyanide from cassava foods indicates that mortality of endemic ataxic polyneuropathy is not associated with exposure to cyanide from cassava foods.

Nonsystemic vasculitic neuropathy: insights from a clinical cohort.

BACKGROUND: Nonsystemic vasculitic neuropathy (NSVN) is an uncommon disorder. Few series with small numbers of patients have been reported. The prognosis and treatment of patients presenting with NSVN remain uninvestigated. The authors sought to address these issues by assembling a large retrospective cohort with extended follow-up. METHODS: All nerve biopsies performed over 20 years were reviewed; cases with definite, probable, or possible vasculitis were segregated for clinical correlation. Patients satisfying clinical criteria for NSVN at presentation were selected. Clinicopathologic, treatment, and outcome measures were analyzed in patients followed for > or = 6 months. RESULTS: A total of 48 patients (30 women, 18 men) with a median of 63 months of follow-up were identified. Most patients (85%) had extensive, overlapping involvement of multiple nerves. Only one had a symmetric polyneuropathy. Most neuropathies (96%) were painful. In 96%, nerve damage was distally accentuated, but most had concurrent proximal weakness. Diagnostic sensitivity was 58% for superficial peroneal nerve/peroneus brevis muscle biopsy and 47% for sural nerve biopsy. Combination corticosteroid/cytotoxic therapy was more effective than corticosteroid monotherapy in inducing remission and improving disability, with trends toward reduced relapses and chronic pain. Treatment with cyclophosphamide for >6 months decreased the relapse rate, which was 46% for all patients. Disease/treatment-related mortality was 10%. Six percent developed cutaneous involvement. Although chronic pain persisted in 60% of survivors, 80% had good outcomes. CONCLUSIONS: NSVN nearly always presents as an asymmetric, distally accentuated, painful, sensorimotor polyneuropathy. Risks for systemic spread and death are small, and, aside from pain, neurologic prognosis is unexpectedly good. Although this was not a randomized controlled trial, combination therapy produced the best outcome in this cohort.

[Critical illness neuropathies]. / Neuropathies de réanimation.

A number of patients admitted to intensive care units for non-neurological disorders develop neuromuscular complications. These patients present with an acute flaccid generalized weakness that may or may not be accompanied by sensory symptoms. There are two main conditions, namely critical illness polyneuropathy and neuromuscular disorder related to the use of neuromuscular blocking agents. These conditions differ in several ways. Critical illness polyneuropathy occurs usually after long stays (weeks) in intensive care units. It concerns patients presenting with a multiple organ dysfunction syndrome, and often sepsis. The polyneuropathy is axonal and implies both sensory and motor fibres. Its pathophysiology remains unclear. Mortality is as high as 60 p.cent and relates to the medical, rather than to the neurological condition. In survivors recovery may be complete, although over a period of months. Neuromuscular disorder related to the use of neuromuscular blocking agents occurs on average after 10 days. It most often concerns patients admitted to intensive care units for acute respiratory failure, mainly asthma or adult respiratory distress syndrome, that may require mechanical ventilation, use of neuromuscular blocking agents and steroids. A purely motor deficit is usually first noticed when curarisation is discontinued. Electromyography discloses fibrillation potentials in all muscles, as well as myopathic changes. Muscle biopsy demonstrates necrosis and a deficit in myosin filaments. In severe cases, injury to distal motor axons probably occurs. Recovery is usually excellent over a few weeks. Recently, replacement of neuromuscular blocking agents by sedatives has notably reduced the occurrence of this disorder. Critical illness neuropathies often cause difficulty in weaning patients from the respirator. They prolong the stay in the intensive care unit, thereby increasing the risks of complications for the patients. Course of these neuromuscular disorders is usually favorable, however sometimes with sequelae.

Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients.

OBJECTIVE: To determine risk factors and clinical consequences of critical illness polyneuropathy (CIP) evaluated by the impact on duration of mechanical ventilation, length of stay and mortality. DESIGN: Inception cohort study. SETTING: Intensive care unit of a tertiary hospital. PATIENTS: Septic patients with multiple organ dysfunction syndrome requiring mechanical ventilation and without previous history of polyneuropathy. INTERVENTIONS: Patients underwent two scheduled electrophysiologic studies (EPS): on the 10th and 21st days after the onset of mechanical ventilation. RESULTS: Eighty-two patients were enrolled, although nine of them were not analyzed. Forty-six of the 73 patients presented CIP on the first EPS and 4 other subjects were diagnosed with CIP on the second evaluation. The APACHE II scores of patients with and without CIP were similar on admission and on the day of the first EPS. However, days of mechanical ventilation [32.3 (21.1) versus 18.5 (5.8); p=0.002], length of ICU and hospital stay in patients discharged alive from the ICU as well as in-hospital mortality were greater in patients with CIP (42/50, 84% versus 13/23, 56.5%; p=0.01). After multivariate analysis, independent risk factors were hyperosmolality [odds ratio (OR) 4.8; 95% confidence intervals (95% CI) 1.05-24.38; p=0.046], parenteral nutrition (OR 5.11; 95% CI 1.14-22.88; p=0.02), use of neuromuscular blocking agents (OR 16.32; 95% CI 1.34-199; p=0.0008) and neurologic failure (GCS below 10) (OR 24.02; 95% CI 3.68-156.7; p<0.001), while patients with renal replacement therapy had a lower risk for CIP development (OR 0.02; 95% CI 0.05-0.15; p<0.001). By multivariate analysis, CIP (OR 7.11; 95% CI 1.54-32.75; p<0.007), age over 60 years (OR 9.07; 95% CI 2.02-40.68; p<0.002) and the worst renal SOFA (OR 2.18; 95% CI 1.27-3.74; p<0.002) were independent predictors of in-hospital mortality. CONCLUSIONS: CIP is associated with increased duration of mechanical ventilation and in-hospital mortality. Hyperosmolality, parenteral nutrition, non-depolarizing neuromuscular blockers and neurologic failure can favor CIP development.