The effects of sugammadex vs. neostigmine on postoperative respiratory complications and advanced healthcare utilisation: a multicentre retrospective cohort study.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

The development and validation of the Score for the Prediction of Postoperative Respiratory Complications (SPORC-2) to predict the requirement for early postoperative tracheal re-intubation: a hospital registry study.

Postoperative pulmonary complications are associated with an increase in mortality, morbidity and healthcare utilisation. The Agency for Healthcare Research and Quality recommends risk assessment for postoperative respiratory complications in patients undergoing surgery. In this hospital registry study of adult patients undergoing non-cardiac surgery between 2005 and 2017 at two independent healthcare networks, a prediction instrument for early postoperative tracheal re-intubation was developed and externally validated. This was based on the development of the Score for Prediction Of Postoperative Respiratory Complications. For predictor selection, stepwise backward logistic regression and bootstrap resampling were applied. Development and validation cohorts were represented by 90,893 patients at Partners Healthcare and 67,046 patients at Beth Israel Deaconess Medical Center, of whom 699 (0.8%) and 587 (0.9%) patients, respectively, had their tracheas re-intubated. In addition to five pre-operative predictors identified in the Score for Prediction Of Postoperative Respiratory Complications, the final model included seven additional intra-operative predictors: early post-tracheal intubation desaturation; prolonged duration of surgery; high fraction of inspired oxygen; high vasopressor dose; blood transfusion; the absence of volatile anaesthetic use; and the absence of lung-protective ventilation. The area under the receiver operating characteristic curve for the new score was significantly greater than that of the original Score for Prediction Of Postoperative Respiratory Complications (0.84 [95%CI 0.82-0.85] vs. 0.76 [95%CI 0.75-0.78], respectively; p < 0.001). This may allow clinicians to develop and implement strategies to decrease the risk of early postoperative tracheal re-intubation.

Effects of low-dose intraoperative fentanyl on postoperative respiratory complication rate: a pre-specified, retrospective analysis.

BACKGROUND: Fentanyl is one of the most frequently administered intraoperative drugs and may increase the risk of postoperative respiratory complications (PRCs). METHODS: We performed a pre-specified analysis of 145 735 adult non-cardiac surgical cases under general anaesthesia. Using multivariable logistic regression, we evaluated the association of intraoperative fentanyl dose and PRCs within 3 days after surgery (defined as reintubation, respiratory failure, pneumonia, pulmonary oedema, or atelectasis). We examined effect modification by patient characteristics, surgical site, and anaesthetics used. RESULTS: PRCs within 3 days after surgery occurred in 18 839 (12.9%) patients. In comparison with high intraoperative fentanyl doses [median: 3.85; inter-quartile range (IQR): 3.42-4.50 µg kg-1, quartile 4 (Q4)], low intraoperative fentanyl dose [median: 0.80, IQR: 0.00-1.14 µg kg-1, quartile 1 (Q1)] was significantly associated with lower odds of PRCs [Q1 vs Q4: 10.9% vs 16.2%; adjusted odds ratio (aOR) 0.79; 95% confidence intervals (CI) 0.75-0.84; P<0.001; adjusted absolute risk difference (aARD) -1.7%]. This effect was augmented by thoracic surgery (P for interaction <0.001; aARD -6.2%), high doses of inhalation anaesthetics (P for interaction=0.016; aARD -2.2%) and neuromuscular blocking agents (NMBAs) (P for interaction=0.001; aARD -3.4%). Exploratory analysis demonstrated that compared with no fentanyl, low-dose fentanyl was associated with lower rates of PRCs (decile 2 vs decile 1: aOR 0.82, CI 0.75-0.89, P<0.001). CONCLUSIONS: Intraoperative low-dose fentanyl (about 60-120 µg for a 70 kg patient) was associated with lower risk of postoperative respiratory complications compared with both no fentanyl and high-dose fentanyl. Beneficial effects of low-dose fentanyl were magnified in specific patient subgroups. CLINICAL TRIAL REGISTRATION: NCT03198208.

The association of early postoperative desaturation in the operating theatre with hospital discharge to a skilled nursing or long-term care facility.

It is unclear which criteria should be used to define readiness for tracheal extubation in the operating theatre. We studied the effects of desaturation in the operating theatre immediately after tracheal extubation on long-term outcomes. Performing a pre-specified, retrospective analysis of 71,025 cases involving previously independent adults undergoing non-cardiac surgery, we evaluated the association between desaturation events (oxygen saturation < 90%) within 10 min of tracheal extubation and adverse discharge (to a skilled nursing facility or long-term care facility). A total of 404 (12.3%) cases with, and 5035 (7.4%) cases without, early postoperative desaturation had an adverse discharge. Early postoperative desaturation was associated with higher odds of being discharged to a nursing facility (adjusted odds ratio 1.36 (95%CI 1.20-1.54); p < 0.001). Increased duration of desaturation augmented the effect (p for trend < 0.001). Desaturation was associated with a higher risk of respiratory, renal and cardiovascular complications as well as increased duration of hospital stay, postoperative intensive care unit admission frequency and cost. Several modifiable factors were associated with desaturation including: high intra-operative long-acting opioid administration; high neostigmine dose; high intra-operative inspired oxygen concentration; and low oxygen delivery immediately before tracheal extubation. There was substantial provider variability between anaesthetists in the incidence of postoperative desaturation unexplained by patient- and procedure-related factors. Early postoperative desaturation is a potentially preventable complication associated with a higher risk of adverse discharge disposition. Anaesthetists may consider developing guidelines to define tracheal extubation readiness that contain postoperative desaturation as an adverse outcome after tracheal extubation.

Implementation of a new strategy to improve the peri-operative management of neuromuscular blockade and its effects on postoperative pulmonary complications.

Inappropriate dosing of neostigmine for antagonism of neuromuscular blockade has been associated with postoperative pulmonary complications. We evaluated the effects of a quality improvement initiative tailored to optimise the use of neostigmine in antagonising neuromuscular blockade on postoperative pulmonary complications, costs and duration of hospital stay. The quality improvement initiative consisted of: a reduction in available neostigmine aliquot sizes; a cognitive aid; an educational component; and a financial incentive for the intra-operative documentation of train-of-four measurement before administration of neostigmine. We conducted a pre-specified analysis of data obtained in our quality improvement study. Additional analyses were conducted in a propensity-matched cohort. An interrupted time series design was used to discriminate between the intervention and a counterfactual scenario. We analysed 12,025 consecutive surgical cases performed in 2015. Postoperative pulmonary complications occurred in 220 (7.5%) of 2937 cases pre-intervention and 568 (6.3%) of 9088 cases post-intervention. Adjusted regression analyses showed significantly a lower risk of postoperative pulmonary complications (OR 0.73 (95%CI 0.61-0.88); p = 0.001), lower costs (incidence rate ratio 0.95 (95%CI 0.93-0.97); p < 0.001) and shorter duration of hospital stay (incidence rate ratio 0.91 (95%CI 0.87-0.94); p < 0.001) after implementation of the quality improvement initiative. Analyses in a propensity-matched sample (n = 2936 per group) and interrupted time series analysis (n = 27,202 cases) confirmed the findings. Our data show that a local, multifaceted quality improvement initiative can enhance the quality of intra-operative neuromuscular blocking agent utilisation, thereby reducing the incidence of postoperative pulmonary complications.

Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England.

BACKGROUND: The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission. METHODS: We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors. RESULTS: Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0-2 vs 3-30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors. CONCLUSIONS: High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery.

Treatment of acute stroke with hyperbaric oxygen: time window for efficacy.

We conducted a retrospective statistical analysis of the Heyman, Saltzman, Whalen 1966 study of 22 stroke patients treated with hyperbaric oxygen (HBO2)--13 of them one to five hours post-stroke. We examined patients who received HBO2 treatment within seven hours post-stroke. An exploratory logistic regression analysis examining the influence of time post-stroke, time in chamber and dose of HBO2, range 2.02 atmospheres absolute (ATA) to 3.04 ATA, was conducted. Only time post-stroke was a significant influence for recovery, with each passing hour decreasing the chance of at least partial transient recovery by 62% - odds ratio: 0.38 (95% CI: 0.15 -0.95), p = 0.039. In the one- to five-hour group of 13 patients, nine (41% of 22) had recovery or recovery with relapse. This represented 69% (+/- 25% SE) of this time frame. Only two of the nine had permanent recovery. Past six hours poststroke, only one patient (11% +/- 21% SE) had partial recovery with relapse. The other eight past six hours had no recovery at all. The first three hours post-stroke HBO2 administration has the most promise for efficacy and improvement of rtPA therapy. HBO2 may also prove to be a useful challenge pre-rtPA administration to assess the risk-benefit ratio for giving rtPA.

Prospective, randomized, single-blind, sham treatment-controlled study of the safety and efficacy of an electromagnetic field device for the treatment of chronic low back pain: a pilot study.

OBJECTIVES: To evaluate the efficacy and safety of therapeutic electromagnetic fields (TEMF) on chronic low back pain. Secondary objectives included the investigation of the effects of TEMF on psychometric measures. SETTING: Pain Research center in an Urban Academic Rehabilitation Facility. DESIGN: Prospective, randomized, single-blind, placebo (sham) treatment-controlled design in which participants were evaluated over a 6-week period. A total of 40 subjects were randomly assigned: 20 subjects to 15 milliTESLA (mT) treatment using a prototype electromagnetic field device and 20 to sham treatment. INTERVENTIONS: After a 2-week baseline period, eligible individuals were randomized to one of the treatment groups (sham or 15 mT) for six 30-minute treatments over 2 weeks, then a 2-week follow-up period. OUTCOME MEASURES: The primary outcome measure was the self-report of pain severity using a 100 mm visual analog scale collected using a twice daily McGill Pain Questionnaire-Short Form. Several secondary measures were assessed. RESULTS: Both groups (15 mT and sham) improved over time (P < 0.05). Although groups were similar during the treatment period, treated subjects (TEMF of 15 mT) improved significantly over sham treatment during the 2-week follow-up period (20.5% reduction in pain; F(1,34) = 10.62, P = 0.003). There were no reported serious adverse events. CONCLUSIONS: This study demonstrates that TEMF may be an effective and safe modality for the treatment of chronic low back pain disorders. More studies are needed to test this hypothesis.

Neuromuscular reflexes contribute to knee stiffness during valgus loading.

We have previously shown that abduction angular perturbations applied to the knee consistently elicit reflex responses in knee joint musculature. Although a stabilizing role for such reflexes is widely proposed, there are as of yet no studies quantifying the contribution of these reflex responses to joint stiffness. In this study, we estimate the mechanical contributions of muscle contractions elicited by mechanical excitation of periarticular tissue receptors to medial-lateral knee joint stiffness. We hypothesize that these reflex muscle contractions will significantly increase knee joint stiffness in the adduction/abduction direction and enhance the overall stability of the knee. To assess medial-lateral joint stiffness, we applied an abducting positional deflection to the fully extended knee using a servomotor and recorded the torque response using a six degree-of-freedom load-cell. EMG activity was also recorded in both relaxed and preactivated quadriceps and hamstrings muscles with surface electrodes. A simple, linear, second-order, delayed model was used to describe the knee joint dynamics in the medial/lateral direction. Our data indicate that excitation of reflexes from periarticular tissue afferents results in a significant increase of the joint's adduction-abduction stiffness. Similar to muscle stretch reflex action, which is modulated with background activation, these reflexes also show dependence on muscle activation. The potential significance of this reflex stiffness during functional tasks was also discussed. We conclude that reflex activation of knee muscles is sufficient to enhance joint stabilization in the adduction/abduction direction, where knee medial-lateral loading arises frequently during many activities.

Identification of a cytoskeleton-bound form of phospholemman with unique C-terminal immunoreactivity.

Phospholemman (PLM) is a 72-amino acid transmembrane protein thought to function in Na,K-ATPase regulation or assembly, similar to other members of the FXYD family of proteins. Unique to PLM among these regulatory proteins are sites for C-terminal phosphorylation by PKA and PKC, although a role for phosphorylation in PLM function remains unclear. To study PLM phosphorylation, we used PLM phosphopeptides to generate antibodies to specifically detect phosphorylated PLM. Peptide affinity chromatography isolated two populations of antibodies: one reacting with standard PLM, a collection of closely-spaced 15-kDa protein bands by SDS-PAGE. About 20% of PLM antibodies reacted specifically with a single distinct form of PLM. Levels of this second immunological form (PLM-b) were increased with overexpression of PLM cDNA, and also reacted with a monoclonal antibody against the PLM N-terminus. In complete contrast to standard PLM, however, PLM-b was quantitatively insoluble in nonionic detergents and was released from tight binding by colchicine. Antibodies to PLM-b were present in two different antisera raised to the phosphorylated C-terminal peptide (residues 57-70), but not in antiserum raised to the non-phosphorylated C-terminal peptide. Despite an apparent relationship between PLM-b and phosphorylated PLM, PLM-b levels were not affected by treatment of heart cells with isoproterenol. PLM-b appears to represent a cytoskeleton-attached detergent-insoluble form of PLM with distinctive C-terminal immunoreactivity that might have implications for PLM structure and function.

Nicotine and caffeine intake in complex regional pain syndrome.

UNLABELLED: {\it OBJECTIVE: } Nicotine and caffeine are vasoconstrictors. Complex regional pain syndrome (CRPS) is defined to involve disproportionate pain and autonomic dysfunction [1]. The objectives of this study were to identify the prevalence of smoking and caffeine intake in CRPS, to explore the relationship of pain intensity with smoking and caffeine consumption, and to explore the relationship of pain intensity, anxiety and disability among CRPS patients who smoke, use caffeine, or both. {\it DESIGN: } One hundred eleven patients, with CRPS type I or II, from two academic rehabilitation pain clinics were reviewed. Data were collected retrospectively by reviewing CRPS patients' self-reported pain level using visual analogue scales (VAS), Beck Depression Inventory (BDI), Pain Disability Index (PDI), and Pain Anxiety Symptoms Scale (PASS). Status of daily smoking and caffeine consumption were also recorded. {\it RESULTS: } Smoking prevalence among CRPS was significant higher than the national average (p < 0.001). There were no significant relationships between the perceived pain level and either daily smoking, daily caffeine intake, or both (p > 0.430). In patients with CRPS I higher PASS scores were positively associated with dichotomous use of smoking and caffeine (p < 0.05). The PASS scores among patients with CRPS~II were not available for analysis. {\it CONCLUSIONS: } The smoking prevalence was higher than the national average among patients with CRPS I and II. Among patients with CRPS~I smoking and caffeine consumption were greater in those who reported more pain-related anxiety, but did not influence pain intensity. The clinical implications of these findings will be discussed.

An examination of the validity of the IHS classification system for migraine and tension-type headache in the college student population.

The validity of the International Headache Society (IHS) classification system for college-aged students with headache was examined using cluster analysis. Undergraduate college student volunteers (N = 369) underwent a structured diagnostic interview for headaches, and the sample was divided into two subsamples for purposes of replication. A hierarchical cluster analysis (Ward's method) of the headache characteristics reported by the first subsample suggested a statistically distinct three-cluster solution, and the solution was replicated using the second subsample. It appeared that one cluster was tensionlike, while the other two were migrainelike. Nonhierarchical cluster analyses (K-means) of the cases from each subsample revealed a similar pattern of a tensionlike and two migrainelike clusters. Identical three-cluster solutions were found for the second subsample both by using cluster centers from the first subsample and by clustering the cases independently, suggesting that the cluster solution was not a random finding. The IHS classification system appears to lack adequate specificity and sensitivity for college-aged students with headache who report migrainelike symptoms. Thus, the generalizability of research results using college-aged students with headache to the adult population may be questionable.

Aspergillosis of the orbit with immunosuppressive therapy.

A case report of aspergillosis of the orbit in a 27-year-old renal transplant patient receiving immunosuppressive therapy is presented. The predominant clinical features were slowly progressive, painful exophthalmos and fever of undetermined origin. Orbital biopsy established the diagnosis. The histopathologic characteristics of the infectious process changed from the time of biopsy to the time of autopsy, reflecting the patient's changing immunologic status.