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Changes in nerve conduction studies occur in the majority of patients early in the course of severe sepsis and predict the development of acquired neuromuscular dysfunction and mortality in intensive care unit patients. Most patients with acquired neuromuscular dysfunction after sepsis have both critical illness myopathy and critical illness neuropathy.

The purpose was to estimate the frequency, characteristics, and risk factors of HIV-associated distal sensory polyneuropathy (DSP) among South Africans who attend an urban community-based clinic. In a cross-sectional study, neuropathy status was determined in 598 HIV-infected adults using validated tools (Brief Peripheral Neuropathy Screen and a modified version of the Total Neuropathy Score) to categorize subjects as DSP versus no DSP. Symptomatic DSP (SDSP) required the presence of at least two neuropathic signs together with symptoms. Clinical, anthropometric, and laboratory evaluations were prospectively performed. CD4 counts, antiretroviral therapy (ART), and questionnaires regarding previous tuberculosis (TB) and alcohol exposure were collected retrospectively. Approximately half (49%) of the study population were diagnosed with DSP, and 30% of the study population were diagnosed with SDSP. In multivariate analyses the odds ratio (OR) (95% confidence interval) of DSP were independently associated with ART use (OR 1.7, 1.0-2.9), age (per 10 year increment) (OR 1.7, 1.4-2.2), and prior TB (OR 2.0, 1.3-3.0). Pain or paresthesias were reported as moderately severe by 70% of those with SDSP. Stavudine use was significantly associated with DSP. DSP is a clinically significant problem in urban HIV-infected Africans. Our findings raise the possibility that the incidence of DSP may be reduced with avoidance of stavudine-containing regimens in older subjects, especially with a history of prior TB infection.

ContributorsGIW wrote and revised the manuscript in response to co-author comments. He finalized all the figures and tables, performed the literature search, and assisted with data interpretation. HJK critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. IBA performed the data analysis, constructed the figures and tables, and made important suggestions to improve the manuscript. H-CK assisted with the data analysis and also reviewed the manuscript. GRC critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. All other authors were given the opportunity to review the manuscript and make suggestions which GIW received, either revising the paper or providing explanations. All who are not deceased were involved with approval of the manuscript.

The development of neuromuscular dysfunction (NMD) during critical illness is increasingly recognized as a cause of failure to wean from mechanical ventilation and is associated with significant morbidity and mortality. At times it is difficult to identify the presence of NMD and distinguish the etiology of the weakness in patients with critical illness, but subtle clinical findings and bedside electrophysiological testing are helpful in establishing the diagnosis. The purpose of this review is to describe the clinical spectrum of acquired neuromuscular weakness in the setting of critical illness, provide an approach to diagnosis, and to discuss its pathogenesis. Finally, we propose defective sodium channel regulation as a unifying mechanism underlying NMD in critically ill patients.

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Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed.

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