Concordance of Sleep and Pain Outcomes of Diverse Interventions: An Umbrella Review

<div><h3>Background/Objective</h3><p>Pain influences sleep and vice versa. We performed an umbrella review of meta-analyses on treatments for diverse conditions in order to examine whether diverse medical treatments for different conditions have similar or divergent effects on pain and sleep.</p> <h3>Methods</h3><p>We searched published systematic reviews with meta-analyses in the Cochrane Database of Systematic Reviews until October 20, 2011. We identified randomized trials (or meta-analyses thereof, when >1 trial was available) where both pain and sleep outcomes were examined. Pain outcomes were categorized as headache, musculoskeletal, abdominal, pelvic, generic or other pain. Sleep outcomes included insomnia, sleep disruption, and sleep disturbance. We estimated odds ratios for all outcomes and evaluated the concordance in the direction of effects between sleep and various types of pain and the correlation of treatment effects between sleep and pain outcomes.</p> <h3>Results</h3><p>151 comparisons with 385 different trials met our eligibility criteria. 96 comparisons had concordant direction of effects between each pain outcome and sleep, while in 55 the effect estimates were in opposite directions (P<0.0001). In the 20 comparisons with largest amount of evidence, the experimental drug always had worse sleep outcomes and tended to have worse pain outcomes in 17/20 cases. For headache and musculoskeletal pain, 69 comparisons showed concordant direction of effects with sleep outcomes and 36 showed discordant direction (P<0.0001). For the other 4 pain types there were overall 27 vs. 19 pairs with concordant vs. discordant direction of effects (P = 0.095). There was a weak correlation of the treatment effect sizes for sleep vs. headache/musculoskeletal pain (r = 0.17, P = 0.092).</p> <h3>Conclusions</h3><p>Medical interventions tend to have effects in the same direction for pain and sleep outcomes, but exceptions occur. Concordance is primarily seen for sleep and headache or musculoskeletal pain where many drugs may both disturb sleep and cause pain.</p> </div

Analyses for primary vs. non-primary outcome.

<p>NA, not applicable.</p

Treatment effects for sleep and pain outcomes for the 20 comparisons with largest amount of evidence^a.

a<p>Amount of evidence is defined by the weight (sum of the inverse variances of the pain and sleep outcome effect sizes), OR>1.00 signifies worse outcome with the experimental versus control treatment.</p><p>SSRIs, selective serotonin reuptake inhibitors; OR, odds ratio; CI, confidence interval:, TCA, tricyclic antidepressants.</p

Correlation between treatment effect size (odds ratio) for sleep vs. headache or musculoskeletal pain.

<p>Not shown are 6 (3 on each type of pain) comparisons that have effects outside the range.</p

Correlations of the effect sizes for sleep versus pain outcomes.

<p>NP, not pertinent, because only two comparisons were available.</p

Correlation between treatment effect size (odds ratio) for sleep vs. any other type of pain outcome.

<p>Not shown are 2 comparisons that have effects outside the range (1 for abdominal pain and 1 for pelvic pain).</p

Bispectral Index Dynamics During Propofol Hypnosis Is Similar in Red-Haired and Dark-Haired Subjects

BACKGROUND: We have previously shown that red hair is associated with increased desflurane requirement for immobility, compared with dark hair. The effect of red hair on IV anesthetic requirement remains unknown. We tested the hypothesis that the propofol concentration in the effect site associated with half maximal electroencephalogram response, Ce-50 is at least 50% higher in subjects with red hair

Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent nocturnal hypoxia and sleep disruption. Sleep fragmentation caused hyperalgesia in volunteers, while nocturnal hypoxemia enhanced morphine analgesic potency in children with OSA. This evidence directly relates to surgical OSA patients who are at risk for airway compromise due to postoperative use of opioids. Using accepted experimental pain models, we characterized pain processing and opioid analgesia in male volunteers recruited based on their risk for OSA.After approval from the Intitutional Review Board and informed consent, we assessed heat and cold pain thresholds and tolerances in volunteers after overnight polysomnography (PSG). Three pro-inflammatory and 3 hypoxia markers were determined in the serum. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 µg/ml), an μ-opioid agonist. Linear mixed effects regression models were employed to evaluate the association of 3 PSG descriptors [wake after sleep onset, number of sleep stage shifts, and lowest oxyhemoglobin saturation (SaO(2)) during sleep] and all serum markers with pain thresholds and tolerances at baseline, as well as their changes under remifentanil.Forty-three volunteers (12 normal and 31 with a PSG-based diagnosis of OSA) were included in the analysis. The lower nadir SaO(2) and higher insulin growth factor binding protein-1 (IGFBP-1) were associated with higher analgesic sensitivity to remifentanil (SaO(2), P = 0.0440; IGFBP-1, P = 0.0013). Other pro-inflammatory mediators like interleukin-1β and tumor necrosis factor-α (TNF-α) were associated with an enhanced sensitivity to the opioid analgesic effect (IL-1β, P = 0.0218; TNF-α, P = 0.0276).Nocturnal hypoxemia in subjects at high risk for OSA was associated with an increased potency of opioid analgesia. A serum hypoxia marker (IGFBP-1) was associated with hypoalgesia and increased potency to opioid analgesia; other pro-inflammatory mediators also predicted an enhanced opioid potency.Clinicaltrials.gov NCT00672737

Neuromuscular Block Differentially Affects Immobility and Cortical Activation at Near-Minimum Alveolar Concentration Anesthesia

BACKGROUND: Anesthesia-induced immobility and cortical suppression are governed by anatomically separate, but interacting, areas of the central nervous system. Consequently, larger volatile anesthetic concentrations are required to suppress cortical activation than to abolish movement in response to noxious stimulation. We examined the effect of decreased afferent input, as produced by neuromuscular block (NMB), on immobility and cortical activation, as measured by Bispectral index (BIS) of the electrocardiogram, in the presence of noxious stimulation during approximately minimum alveolar concentrations (MACs) of desflurane anesthesia