We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid antiobsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n ¼ 15) with nearconstant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (po0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n ¼ 8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n ¼ 7). One-week post-infusion, 50% of those receiving ketamine (n ¼ 8) met criteria for treatment response (X35% Y-BOCS reduction) vs 0% of those receiving placebo (n ¼ 7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.

Studies using molecular modeling, genetic engineering, neurophysiology/pharmacology, and whole animals have advanced our understanding of where and how inhaled anesthetics act to produce immobility (minimum alveolar anesthetic concentration; MAC) by actions on the spinal cord. Numerous ligand- and voltage-gated channels might plausibly mediate MAC, and specific amino acid sites in certain receptors present likely candidates for mediation. However, in vivo studies to date suggest that several channels or receptors may not be mediators (e.g., gamma-aminobutyric acid A, acetylcholine, potassium, 5-hydroxytryptamine-3, opioids, and alpha(2)-adrenergic), whereas other receptors/channels (e.g., glycine, N-methyl-D-aspartate, and sodium) remain credible candidates.

Objective To define the amount of opioid analgesics prescribed and consumed after discharge after cesarean delivery. Methods We conducted a survey at six academic medical centers in the United States from 9/2014 to 3/2016. Women who had undergone a cesarean delivery were contacted by phone two weeks after discharge and participated in a structured interview about the opioid prescription they received upon discharge and their oral opioid intake while at home. Results A total of 720 women were enrolled; of these, 615 (85.4%) filled an opioid prescription. The median number of dispensed opioid tablets was 40 (interquartile range (IQR) 30 to 40), the median number consumed was 20 (IQR 8 to 30), and leftover was 15 (IQR 3 to 26). Of those with leftover opioids, 95.3% had not disposed of the excess medication at the time of the interview. There was an association between a larger number of tablets dispensed and the number consumed independent of patient characteristics. The amount of opioids dispensed did not correlate with patient satisfaction, pain control, or the need to refill the opioid prescription. Conclusion The amount of opioid prescribed after cesarean delivery generally exceeds the amount consumed by a significant margin, leading to substantial amounts of leftover opioid medication. Lower opioid prescription correlates with lower consumption without a concomitant increase in pain scores or satisfaction.

Surgery during pregnancy is complicated by the need to balance the requirements of two patients. Under usual circumstances, surgery is only conducted during pregnancy when it is absolutely necessary for the wellbeing of the mother, fetus, or both. Even so, the outcome is generally favourable for both the mother and the fetus. All general anaesthetic drugs cross the placenta and there is no optimal general anaesthetic technique. Neither is there convincing evidence that any particular anaesthetic drug is toxic in humans. There is weak evidence that nitrous oxide should be avoided in early pregnancy due to a potential association with pregnancy loss with high exposure. There is evidence in animal models that many general anaesthetic techniques cause inappropriate neuronal apoptosis and behavioural deficits in later life. It is not known whether these considerations affect the human fetus but studies are underway. Given the general considerations of avoiding fetal exposure to unnecessary medication and potential protection of the maternal airway, regional anaesthesia is usually preferred in pregnancy when it is practical for the medical and surgical condition. When surgery is indicated during pregnancy maintenance of maternal oxygenation, perfusion and homeostasis with the least extensive anaesthetic that is practical will assure the best outcome for the fetus.

The CNS-type nAChRs are differentially affected by isoflurane and propofol. The alpha 4 beta 2 receptor is affected by isoflurane more potently than the most sensitive GABAA or glycine receptor that has been reported, whereas the alpha 7 homomeric receptor is not affected by either anesthetic. Inhibition of specific subtypes of nAChRs in the CNS, along with potentiation of GABAA and glycine receptors, may contribute to the effects and side effects of general anesthetics.

BackgroundNicotine and nicotinic acetylcholine receptors (nAChRs) have been explored for the past three decades as targets for pain control. The aim of this review is to introduce readers particularly to α7 nAChRs in a perspective of pain and its modulation.MethodsDevelopments for α7 nAChR modulators and recent animal studies related to pain are reviewed.ResultsAccumulating evidences suggest that selective ligands for α7 nAChRs hold promise in the treatment of chronic pain conditions as they lack many of side effects associated with other nicotinic receptor types.ConclusionThis review provides the reader recent insights on α7 nAChRs from structure and function to the latest findings on the pharmacology and therapeutic targeting of these receptors for the treatment of pain and inflammation.

The risks associated with prescription opioids are well described. 1,2 Although reducing opioid use is a national priority, existing opioid tapering models use costly interdisciplinary teams that are largely inaccessible to patients and their physicians. 3,4 Patients and physicians need solutions to successfully reduce long-term prescription opioid dosages in settings without behavioral services. We conducted a study of voluntary, patient-centered opioid tapering in outpatients with chronic pain without behavioral treatment.