Association of Intravenous Neostigmine and Anticholinergics or Sugammadex with Postoperative Delirium: A Retrospective Cohort Study.

BACKGROUND: Administration of cholinesterase inhibitors in combination with anticholinergic drugs for reversal of neuromuscular blocks may precipitate delirium through impairment of central cholinergic transmission, which could be avoided by using sugammadex. Therefore, we tested the primary hypothesis that postoperative delirium is less common when neuromuscular block is reversed with sugammadex than with neostigmine combined with glycopyrrolate or atropine. METHODS: We conducted a single-center retrospective cohort study, analyzing all adult patients having general anesthesia for noncardiac surgery who received neostigmine or sugammadex from January 2016 to March 2022. Inverse propensity score weighting and propensity score calibration were used to adjust for appropriate confounders. Our primary outcome was presence of delirium within the first 4 days after surgery, defined as at least 1 positive brief Confusion Assessment Method (bCAM) screening. The secondary outcome was the presence of early delirium within 24 hours of surgery. RESULTS: Among 49,468 cases in our analysis, 6881 received sugammadex and 42,587 received neostigmine. After propensity weighting, the incidence of delirium was 1.09% in the sugammadex group and 0.82% in the neostigmine group. The odds of postoperative delirium did not differ between the sugammadex and neostigmine groups, with an estimated odds ratio (95% confidence interval) of 1.33 (0.91-1.95), P = .147. A sensitivity analysis restricted to only include cases with at least 6 bCAM measurements over postoperative day (POD) 1 to 4 had consistent results, as sugammadex compared with neostigmine was associated with an estimated odds ratio for postoperative delirium of 1.20 (0.82-1.77), P = .346. Sugammadex was significantly associated with an increased incidence of early postoperative delirium, with an estimated odds ratio of 1.71 (1.07-2.72), P = .025. Further analysis showed no treatment-by-age interaction for either postoperative delirium (P = .637) or postoperative early delirium (P = .904). CONCLUSIONS: Compared to neostigmine, use of sugammadex for reversal of neuromuscular block was not associated with an increased risk of postoperative delirium in this retrospective single-center study. Though sugammadex was associated with a statistically significant increased risk of postoperative early delirium, the difference was small and not clinically relevant, and may reflect the presence of unknown confounders.

Metformin Use in Type 2 Diabetics and Delirium After Noncardiac Surgery: A Retrospective Cohort Analysis.

INTRODUCTION: The cause of postoperative delirium is unknown, but it is thought to result at least in part from inflammation. Metformin, besides its hypoglycemic properties, demonstrates anti-inflammatory effects systemically and in the brain. We tested the primary hypothesis that chronic metformin use in adults with type 2 diabetes is associated with less delirium during the first 5 days after major noncardiac surgery. Secondary outcomes were a composite of serious complications (myocardial infarction, cardiac arrest, stage 2-3 acute kidney injury [AKI], and mortality) and time to discharge alive. METHODS: We considered adults with type 2 diabetes who did or did not routinely use metformin daily and had noncardiac surgery. Delirium was assessed by Confusion Assessment Method for Intensive Care Unit (CAM-ICU) or brief Confusion Assessment Method (bCAM) for 5 postoperative days. Postoperative AKI was defined by Kidney Disease Improving Global Guidelines. Logistic regression and generalized estimating equation models accounted for within-patient correlation across multiple surgeries and explored the association between metformin use and postoperative delirium and complications. Inverse propensity score weighting and propensity score calibration (PSC) adjusted for confounding variables. RESULTS: No significant difference was observed in the incidence of postoperative delirium between the 2 groups, with 260 of 4744 cases (5.5%) among metformin users and 502 of 5918 cases (8.5%) cases in nonmetformin users, for an odds ratio of 0.88 (95% confidence interval [CI], 0.73-1.05; P = .155), number-needed-to-expose = 118 patients. Similarly, there were fewer composite complications in metformin users (3.3%) than in nonusers (11.7%); However, the common-effect odds ratio of 0.67 was not statistically significant (97.5% CI, 0.39-1.17; P = .106). Discharge from the hospital was significantly faster in patients who took metformin (3 [interquartile range, IQR, 1-5] days for metformin users and 3 [IQR, 2-6] days for nonmetformin users), with a hazard ratio of 1.07 for early discharge, and tight CIs (1.01-1.13). CONCLUSIONS: Chronic metformin use was associated with slightly and nonsignificantly less delirium. However, patients who used metformin had clinically meaningfully fewer major complications, mostly stage 2 to 3 kidney injury. While not statistically significant, the reduction was substantial and warrants further investigation because there is currently no effective preventive measure for perioperative renal injury. Benefit would be especially meaningful if it could be produced by acute perioperative treatment. Finally, metformin was associated with faster hospital discharge, although not by a clinically meaningful amount.

Postoperative Risk of Transfusion After Reversal of Residual Neuromuscular Block With Sugammadex Versus Neostigmine: A Retrospective Cohort Study.

BACKGROUND: Sugammadex and neostigmine are routinely used to reverse residual neuromuscular blocks at the end of surgery. Sugammadex has been linked with prolongation of laboratory coagulation markers, but clinical relevance on postoperative blood loss and transfusions remains unclear. METHODS: In this retrospective, single-center, cohort study, we analyzed medical records of adult patients having noncardiac surgery who were given sugammadex or neostigmine from May 2016 to December 2020. Our primary outcome was the incidence of any postoperative transfusion of red blood cells, and/or fresh-frozen plasma, and/or platelets. Secondary outcomes were duration of hospitalization, need for resurgery, and postoperative intensive care unit (ICU) admission. After propensity score weighting, the odds ratio (OR) for postoperative transfusion was assessed in both groups (sugammadex versus neostigmine) using a generalized estimation equation to count within-subject correlation weighted by the inverse propensity score. RESULTS: Out of 39,325 eligible surgeries, 33,903 surgeries in 29,062 patients were included in the analysis; with 4581 patients receiving sugammadex and 29,322 patients receiving neostigmine. The raw incidence of postoperative transfusion was 7.40% in sugammadex and 7.45% in the neostigmine group. After weighting by propensity score, the incidence of postoperative transfusion was 8.01% in the sugammadex and 7.38% in the neostigmine group (OR, 1.11 [95% confidence interval [CI], 0.97-1.26; P = .118]). There was no difference in duration of hospitalization and need for resurgery, but odds of postoperative ICU admission were significantly higher for patients receiving sugammadex than those receiving neostigmine (OR, 1.33 [98.33% CI, 1.17-1.52; P < .0001]). Our a priori planned analysis of coagulation laboratory parameters could not be completed because of a high amount of missing laboratory data. CONCLUSIONS: There is no statistically significant nor clinically important difference in the risk of postoperative transfusion in patients receiving sugammadex or neostigmine.

The Role of Sex Hormones in Pain-Related Conditions.

Millions of people are affected by pain-related conditions worldwide. Literature has consistently shown that each individual experiences and perceives pain in a unique manner due to biological, environmental, and cultural factors in which they have been raised. It has been established that biological males and females perceive pain differently and that it may be partially explained by their distinct hormonal profiles since birth, which are only further magnified during puberty. For biological males, high levels of testosterone have shown to increase their pain threshold; and for biological females, estrogen fluctuations have shown to increase pain intensity and perception. However, sex hormones have not been studied in the context of pain treatment or their impact on biochemical pathways involved in pain perception. For this purpose, the transgender community serves as a unique population to investigate the impact of hormone replacement therapy on molecular pathways involved in the perception of pain. The purpose of this review is to explore the biochemistry of hormone replacement in transgender patients who also have other pain-related conditions such as headaches, fibromyalgia, temporomandibular myalgia, and visceral pain.

Development, Validation, and Results of a Survey of Personal Electronic Device Use Among 299 Anesthesia Providers From a Single Institution.

BACKGROUND: The pattern of perioperative use of personal electronic devices (PEDs) among anesthesia providers in the United States is unknown. METHODS: We developed a 31-question anonymous survey of perioperative PED use that was sent to 813 anesthesiologists, anesthesiology residents, and certified registered nurse anesthetists at 3 sites within one health system. The electronic survey assessed patterns of PED use inside the operating room (OR), outside the OR, and observed in others. Questions were designed to explore the various purposes for PED use, the potential impact of specific hospital policies or awareness of medicolegal risk on PED use, and whether PED was a source of perioperative distraction. RESULTS: The overall survey response rate was 36.8% (n = 299). With regard to often/frequent PED activity inside the OR, 24% reported texting, 5% reported talking on the phone, and 11% reported browsing on the Internet. With regard to often/frequent PED activity outside the OR, 88% reported texting, 26% reported talking on the phone, and 63% reported browsing the Internet. With regard to often/frequent PED activity observed in others, 52% reported others texting, 14% reported others talking on the phone, and 34% reported others browsing the Internet. Two percent of respondents self-reported a distraction compared to 15% who had observed a distraction in others. Eighty percent of respondents recognized PED as a potential distraction for patient safety. CONCLUSIONS: Our data reinforce that PED use is prevalent among anesthesia providers.

Sugammadex use in patients with end-stage renal disease: a historical cohort study.

PURPOSE: While sugammadex (SGX) is not approved for use in patients with end-stage renal disease (ESRD), its administration in this patient population has been reported. We designed the current study to review all instances of patients with ESRD receiving SGX and to describe their clinical outcomes. METHODS: This is a historical cohort study of 219 patients with chronic kidney disease stage 5 who received SGX in one of three hospital locations within the same academic health system. Data were collected between 7 March 2016 and 1 August 2019 and included demographics, notable events from the anesthesia records, and postoperative complications. The primary outcome included any complication possibly related to SGX such as hypersensitivity reactions, need for reintubation, hypoxemia, pneumonia, and residual neuromuscular blockade. Secondary outcomes included any other complication not included in the primary outcome and/or patient mortality within 30 days after the procedure. RESULTS: No patient experienced a hypersensitivity reaction. Three patients required reintubation while two patients developed hypoxemia that did not require reintubation. One patient developed hospital-acquired pneumonia. Fifty (23%) patients developed other postoperative complications (different from our primary outcome) and nine patients (4%) died during the subsequent 30 postoperative days. None of the primary or secondary outcomes appeared to be related to SGX use. CONCLUSIONS: We provide incremental evidence that SGX could be considered as an alternative neuromuscular blockade reversal agent in patients with ESRD.

RéSUMé: OBJECTIF : Bien que le sugammadex (SGX) ne compte pas parmi ses indications une utilisation chez les patients atteints d'insuffisance rénale terminale (IRT), son administration à cette population de patients est rapportée. Nous avons conçu cette étude afin de passer en revue tous les cas de patients atteints d'IRT ayant reçu du SGX et décrire leurs devenirs cliniques. MéTHODE : Il s'agit d'une étude de cohorte historique portant sur 219 patients atteints d'insuffisance rénale chronique de stade 5 ayant reçu du SGX dans l'un de trois hôpitaux appartenant au même réseau de santé universitaire. Les données démographiques, les événements significatifs notés dans les dossiers anesthésiques et les complications postopératoires ont été colligés entre le 7 mars 2016 et le 1er août 2019. Le critère d'évaluation principal incluait toute complication possiblement liée à l'utilisation de SGX telle qu'une réaction d'hypersensibilité, une réintubation, une hypoxémie, une pneumonie, et un bloc neuromusculaire résiduel. Les critères d'évaluation secondaires comprenaient toute autre complication non incluse dans notre critère d'évaluation principal et/ou la mortalité des patients dans les 30 jours suivant l'intervention. RéSULTATS : Aucun patient n'a eu de réaction d'hypersensibilité. Trois patients ont dû être réintubés, et deux patients ont développé une hypoxémie qui n'a pas nécessité de réintubation. Un patient a contracté une pneumonie nosocomiale. Cinquante (23 %) patients ont souffert d'autres complications postopératoires (différentes de notre critère d'évaluation principal) et neuf patients (4 %) sont décédés au cours des 30 jours postopératoires subséquents. Aucun de nos critères d'évaluation primaire ou secondaires ne semblaient liés à l'utilisation de SGX. CONCLUSION : Nous proposons des données probantes supplémentaires selon lesquelles le SGX pourrait être envisagé comme agent décurarisant alternatif chez les patients atteints d'IRT.

An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens.

Ovarian hormones play an important role in pain perception, and are responsible, at least in part, for the pain threshold differences between the sexes. Modulation of pain and its perception are mediated by neurochemical changes in several pathways, affecting both the central and peripheral nervous systems. One of the most studied neurotransmitters related to pain disorders is serotonin. Estrogen can modify serotonin synthesis and metabolism, promoting a general increase in its tonic effects. Studies evaluating the relationship between serotonin and disorders such as irritable bowel syndrome, fibromyalgia, migraine, and other types of headache suggest a clear impact of this neurotransmitter, thereby increasing the interest in serotonin as a possible future therapeutic target. This literature review describes the importance of substances such as serotonin and ovarian hormones in pain perception and illustrates the relationship between those two, and their direct influence on the presentation of the aforementioned pain-related conditions. Additionally, we review the pathways and receptors implicated in each disorder. Finally, the objective was to stimulate future pharmacological research to experimentally evaluate the potential of serotonin modulators and ovarian hormones as therapeutic agents to regulate pain in specific subpopulations.

An appraisal of neostigmine versus sugammadex for neuromuscular blockade reversal in patients with a prior heart transplant.

INTRODUCTION: Heart transplant recipients present unique perioperative challenges for surgery. Specifically, autonomic system denervation has significant implications for commonly used perioperative drugs. This study investigates neuromuscular blocking antagonists in this population when undergoing subsequent non-cardiac surgery. MATERIAL AND METHODS: A retrospective review was performed for the period 2015-2019 across our health care enterprise. Patients with previous orthotopic heart transplant and subsequent non-cardiac surgery were identified. A total of 185 patients were found, 67 receiving neostigmine (NEO) and 118 receiving sugammadex (SGX). Information of patient characteristics, prior heart transplant, and subsequent non-cardiac surgery was collected. Our primary outcome was the incidence of bradycardia (heart rate < 60 bpm) and/or hypotension (mean blood pressure (MAP) < 65 mmHg) following neuromuscular blockade reversal. Secondary outcomes included need of intra-operative inotropic agents, arrhythmia, cardiac arrest, hospital length of stay (hLOS), ICU admission, and death within 30 postoperative days. RESULTS: In unadjusted analysis, no significant differences were found between the two groups in change in heart rate [0 (-26, 14) vs. 1 (-19, 10), P = 0.59], change in MAP [0 (-22, 28) vs. 0 (-40, 47), P = 0.96], hLOS [2 days (1, 72) vs. 2 (0, 161), P = 0.92], or intraoperative hypotension [4 (6.0%) vs. 5 (4.2%), OR = 0.70, P = 0.60] for NEO and SGX respectively. After multivariable analysis, the results were similar for change in heart rate ( P = 0.59) and MAP ( P = 0.90). CONCLUSIONS: No significant differences in the incidence of bradycardia and hypotension were found in the NEO versus SGX groups. NEO and SGX may have similar safety profiles in patients with prior heart transplant undergoing non-cardiac surgery.

Parasagittal Approach of Epidural Steroid Injection as a Treatment for Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

Background: Epidural steroid injection (ESI) has proven benefits in controlling chronic low back pain and can be performed via the midline interlaminar (MIL) or transforaminal (TF) approach. A modified interlaminar approach, the parasagittal interlaminar (PIL), has surfaced as a more reliable, safe, and suitable approach to minimize complications related to MIL and TF. Objective: To conduct a systematic review and meta-analysis to assess and compare the effectiveness and safety of PIL with both MIL and TF approaches in adult patients with a history of chronic low back pain. Methods: A literature search was conducted using major electronic databases, such as PubMed, EMBASE, and Cochrane. Selected studies included patients with unilateral radicular symptoms, secondary to lumbar intervertebral disc hernias or degenerative lumbar disc disease, that, additionally, received ESIs via PIL or either MIL or TF under fluoroscopic guidance. Randomized and observational studies with pain relief score and/or functional disability assessment and at least a 2-week follow-up were included. Results: The search led to the initial identification of 174 studies. Following the screening, eight studies were included in the qualitative analysis and seven randomized controlled trials (RCTs) were included in the statistical analysis. PIL showed statistically significantly more pain relief and functional improvement than MIL at 1-, 3-, and 6-month post-procedure. Compared to TF, PIL showed statistically significantly more pain relief at 3- and 6-month after the procedure. Additionally, PIL showed benefits in terms of lower mean fluoroscopy time, less radiation exposure, zero adverse events in all the included studies, no cases of intravascular spread compared with the TF approach, and a higher anterior epidural spread (AES) of PIL compared with TF. Conclusions: Our systematic review and meta-analysis suggest that the PIL approach is an effective and safe alternative to the MIL and TF approaches in patients presenting with chronic low back pain when epidural injections are indicated, demonstrating a higher level of pain relief and a stronger improvement in functionality post-procedure.

Perioperative duloxetine for acute postoperative analgesia: a meta-analysis of randomized trials.

BACKGROUND: Multimodal analgesia is a fundamental part of modern surgery and enhanced recovery pathways. Duloxetine, a serotonin and norepinephrine reuptake inhibitor, has been validated for the treatment of chronic neuropathic pain. The evidence for duloxetine as an adjunct for the treatment of acute postoperative pain remains controversial. We conducted a meta-analysis to determine the efficacy of duloxetine in the acute perioperative setting. METHODS: A literature search was conducted in the major databases (PubMed, EMBASE and Google Scholar) for randomized controlled trials (RCTs) evaluating duloxetine compared with placebo control for acute postoperative pain. The primary outcome was postoperative pain assessed at 2, 4, 6, 24 and 48 hours time frames. Secondary outcomes included postoperative opioid administration, as well as side effects, such as postoperative nausea/vomiting (PONV), pruritus, dizziness and headache. RESULTS: 574 patients (n=9 RCTs) were included in the analysis, divided between duloxetine (n=285 patients) and placebo (n=289 patients). Duloxetine use was associated with a significant reduction in pain scores as early as 4 (mean difference (MD) -0.9, 95% CI -1.33 to -0.47) and as late as 48 (MD -0.94, 95% CI -1.56 to -0.33) hours postoperatively compared with placebo. In addition, duloxetine was associated with a significant reduction in opioid administration at 24 (standardized MD (SMD) -2.24, 95% CI -4.28 to -0.19) and 48 (SMD -2.21, 95% CI -4.13 to -0.28) hours as well as a significant reduction in PONV (risk ratio 0.69, 95% CI 0.49 to 0.95, p=0.03) compared with placebo. There was no difference between groups in other side effects. CONCLUSION: Duloxetine, a non-opioid neuromodulator, may provide efficacy for the treatment of acute perioperative pain. Additional prospective studies are required to establish optimal perioperative dosing regimens, role in the setting of a comprehensive multimodal analgesic plan and impact on chronic postsurgical pain. PROSPERO REGISTRATION NUMBER: CRD42019121416.

Pineal gliosarcoma in a 5-year-old girl.

The purpose of this paper is to report a rare case of a pediatric pineal gliosarcoma. Gliomas on the pineal region are uncommon, representing 0.4%-1% of all brain tumors. Furthermore, pediatric gliosarcomas are a very rare entity. We present a case of a 5-year-old girl, with a history of headache, vomiting, diplopia, and gait disturbances. A pineal tumor was found with pathology results consistent with a gliosarcoma. A total of 25 cases of pediatric gliosarcomas have been reported, none of them in pineal topography. Only 3 gliosarcomas were found in the pineal region, but these were found in adults. To our knowledge, this is the first pediatric pineal gliosarcoma reported in the literature.