Mechanisms and Preventative Strategies for Persistent Pain following Knee and Hip Joint Replacement Surgery: A Narrative Review.

Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is a prevalent complication of joint replacement surgery which has the potential to decrease patient satisfaction, increase financial burden, and lead to long-term disability. The identification of risk factors for CPSP following TKA and THA is challenging but essential for targeted preventative therapy. Recent meta-analyses and individual studies highlight associations between elevated state anxiety, depression scores, preoperative pain, diabetes, sleep disturbances, and various other factors with an increased risk of CPSP, with differences observed in prevalence between TKA and THA. While the etiology of CPSP is not fully understood, several factors such as chronic inflammation and preoperative central sensitization have been identified. Other potential mechanisms include genetic factors (e.g., catechol-O-methyltransferase (COMT) and potassium inwardly rectifying channel subfamily J member 6 (KCNJ6) genes), lipid markers, and psychological risk factors (anxiety and depression). With regards to therapeutics and prevention, multimodal pharmacological analgesia, emphasizing nonopioid analgesics like acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), has gained prominence over epidural analgesia. Nerve blocks and local infiltrative anesthesia have shown mixed results in preventing CPSP. Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, exhibits antihyperalgesic properties, but its efficacy in reducing CPSP is inconclusive. Lidocaine, an amide-type local anesthetic, shows tentative positive effects on CPSP. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have mixed results, while gabapentinoids, like gabapentin and pregabalin, present hopeful data but require further research, especially in the context of TKA and THA, to justify their use for CPSP prevention.

Incidence of postoperative opioid-induced respiratory depression episodes in patients on room air or supplemental oxygen: a post-hoc analysis of the PRODIGY trial.

BACKGROUND: Supplemental oxygen (SO) potentiates opioid-induced respiratory depression (OIRD) in experiments on healthy volunteers. Our objective was to examine the relationship between SO and OIRD in patients on surgical units. METHODS: This post-hoc analysis utilized a portion of the observational PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial dataset (202 patients, two trial sites), which involved blinded continuous pulse oximetry and capnography monitoring of postsurgical patients on surgical units. OIRD incidence was determined for patients receiving room air (RA), intermittent SO, or continuous SO. Generalized estimating equation (GEE) models, with a Poisson distribution, a log-link function and time of exposure as offset, were used to compare the incidence of OIRD when patients were receiving SO vs RA. RESULTS: Within the analysis cohort, 74 patients were always on RA, 88 on intermittent and 40 on continuous SO. Compared with when on RA, when receiving SO patients had a higher risk for all OIRD episodes (incidence rate ratio [IRR] 2.7, 95% confidence interval [CI] 1.4-5.1), apnea episodes (IRR 2.8, 95% CI 1.5-5.2), and bradypnea episodes (IRR 3.0, 95% CI 1.2-7.9). Patients with high or intermediate PRODIGY scores had higher IRRs of OIRD episodes when receiving SO, compared with RA (IRR 4.5, 95% CI 2.2-9.6 and IRR 2.3, 95% CI 1.1-4.9, for high and intermediate scores, respectively). CONCLUSIONS: Despite oxygen desaturation events not differing between SO and RA, SO may clinically promote OIRD. Clinicians should be aware that postoperative patients receiving SO therapy remain at increased risk for apnea and bradypnea. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02811302, registered June 23, 2016.

Frailty: the perioperative and anesthesia challenges of an emerging pandemic.

Frailty is a complex and multisystem biological process characterized by reductions in physiological reserve. It is an increasingly common phenomena in the surgical population, and significantly impacts postoperative recovery. In this review, we will discuss the pathophysiology of frailty, as well as preoperative, intraoperative, and postoperative considerations for frailty care. We will also discuss the different models of postoperative care, including enhanced recovery pathways, as well as elective critical care admission. With discoveries of new effective interventions, and advances in healthcare information technology, optimized pathways could be developed to provide the best care possible that meets the challenges of perioperative frailty.

Brain Prehabilitation for Oncologic Surgery.

PURPOSE OF REVIEW: This review aims to summarize the current research on postoperative cognitive complications, such as delirium and cognitive dysfunction. This includes discussion on preoperative preventive strategies, such as physical and nutritional prehabilitation as well as up-to-date information on neuroprehabilitation. RECENT FINDINGS: Current recommendations for prevention of postoperative delirium have focused on multicomponent interventions. The optimal composition of surgical prehabilitation programs targeting exercise and nutrition has not yet been established. The Neurobics Trial shows that cognitive prehabilitation improves cognitive reserve and may be a useful addition to multimodal surgical prehabilitation. Perioperative management of oncologic patients is often associated with a myriad of challenges, such as the management of tumor-related pathologies, adverse events from neoadjuvant therapy, and chronic metabolic and immunological changes associated with malignancy. In addition, oncologic patients are at increased risk of developing frailty, which adversely affects postoperative recovery and further cancer treatment. As a result, oncologic patients are at considerable risk of developing postoperative cognitive complications, such as delirium and cognitive dysfunction. In this review, we discuss the effect of prehabilitation on postoperative cognitive outcomes.

Frequency and Temporal Distribution of Postoperative Respiratory Depressive Events.

BACKGROUND: The frequency and temporal distribution of postoperative respiratory depression (RD) events are not completely understood. This study determined the temporal distribution and frequency of RD episodes in postsurgical patients continuously monitored by bedside capnography and pulse oximetry. METHODS: This was a post hoc study of a subset of postsurgical patients enrolled in The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial from 2 sites in the United States. These patients had undergone continuous bedside monitoring on general care wards. These data were adjudicated for potential RD episodes. The number of RD episodes per patient and the time of each RD episode were determined. The first RD episode experienced by a patient was classified as an "initial" episode, and the initial and all subsequent RD episodes experienced by a patient were classified as "all" episodes. A PRODIGY risk score was calculated. RESULTS: Data analyzed from 250 patients contained 2539 RD episodes in 155 (62.0%, 95% confidence interval, 55.7-68.0) patients with median 2 [0-8], range of 0-545 RD episodes per patient, with a PRODIGY risk score distribution of 100 (40.0%) low, 79 (31.6%) intermediate, 70 (28.0%) high (missing data from 1 patient). Median time to the initial RD episode was 8.8 [5.1-18.0] hours postoperatively. There was a peak occurrence of initial RD events between 14:00 and 20:00 on the day of surgery, and these were associated with a large number of subsequent events in the same timeframe. The peak time of all RD episodes occurred from 02:00 to 06:00. Patients with high PRODIGY risk scores had higher incidence and greater number of RD episodes per patient (P < .001, overall comparisons between groups for both incidence [χ2] and number of episodes [Kruskal-Wallis test]). CONCLUSIONS: Continuous monitoring of surgical patients demonstrates that RD episodes are common, and risk increases with higher PRODIGY scores. In this patient cohort, the rate of initial RD episodes peaked in the afternoon to early evening, while peak rate of all RD episodes occurred in early morning. Further, among patients with RD episodes, the number of episodes increased with higher PRODIGY scores.

Opioid-induced respiratory depression increases hospital costs and length of stay in patients recovering on the general care floor.

BACKGROUND: Opioid-induced respiratory depression is common on the general care floor. However, the clinical and economic burden of respiratory depression is not well-described. The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial created a prediction tool to identify patients at risk of respiratory depression. The purpose of this retrospective sub-analysis was to examine healthcare utilization and hospital cost associated with respiratory depression. METHODS: One thousand three hundred thirty-five patients (N = 769 United States patients) enrolled in the PRODIGY trial received parenteral opioids and underwent continuous capnography and pulse oximetry monitoring. Cost data was retrospectively collected for 420 United States patients. Differences in healthcare utilization and costs between patients with and without ≥1 respiratory depression episode were determined. The impact of respiratory depression on hospital cost per patient was evaluated using a propensity weighted generalized linear model. RESULTS: Patients with ≥1 respiratory depression episode had a longer length of stay (6.4 ± 7.8 days vs 5.0 ± 4.3 days, p = 0.009) and higher hospital cost ($21,892 ± $11,540 vs $18,206 ± $10,864, p = 0.002) compared to patients without respiratory depression. Patients at high risk for respiratory depression, determined using the PRODIGY risk prediction tool, who had ≥1 respiratory depression episode had higher hospital costs compared to high risk patients without respiratory depression ($21,948 ± $9128 vs $18,474 ± $9767, p = 0.0495). Propensity weighted analysis identified 17% higher costs for patients with ≥1 respiratory depression episode (p = 0.007). Length of stay significantly increased total cost, with cost increasing exponentially for patients with ≥1 respiratory depression episode as length of stay increased. CONCLUSIONS: Respiratory depression on the general care floor is associated with a significantly longer length of stay and increased hospital costs. Early identification of patients at risk for respiratory depression, along with early proactive intervention, may reduce the incidence of respiratory depression and its associated clinical and economic burden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02811302 .

Tracheobronchial Slough, a Potential Pathology in Endotracheal Tube Obstruction in Patients With Coronavirus Disease 2019 (COVID-19) in the Intensive Care Setting.

BACKGROUND: A novel coronavirus (COVID-19) erupted in the latter part of 2019. The virus, SARS-CoV-2 can cause a range of symptoms ranging from mild through fulminant respiratory failure. Approximately 25% of hospitalized patients require admission to the intensive care unit, with the majority of those requiring mechanical ventilation. High density consolidations in the bronchial tree and in the pulmonary parenchyma have been described in the advanced phase of the disease. We noted a subset of patients who had a sudden, significant increase in peak airway, plateau and peak inspiratory pressures. Partial or complete ETT occlusion was noted to be the culprit in the majority of these patients. METHODS: With institutional IRB approval, we examined a subset of our mechanically ventilated COVID-19 patients. All of the patients were admitted to one of our COVID-19 ICUs. Each was staffed by a board certified intensivist. During multidisciplinary rounds, all arterial blood gas (ABG) results, ventilator settings and ventilator measurements are discussed and addressed. ARDSNet Protocols are employed. In patients with confirmed acute occlusion of the endotracheal tube (ETT), acute elevation in peak airway and peak inspiratory pressures are noted in conjunction with desaturation. Data was collected retrospectively and demographics, ventilatory settings and ABG results were recorded. RESULTS: Our team has observed impeded ventilation in intubated patients who are several days into the critical course. Pathologic evaluation of the removed endotracheal tube contents from one of our patients demonstrated a specimen consistent with sloughed tracheobronchial tissues and inflammatory cells in a background of dense mucin. Of 110 patients admitted to our adult COVID-19 ICUs, 28 patients required urgent exchange of their ETT. CONCLUSION: Caregivers need to be aware of this pathological finding, recognize, and to treat this aspect of the COVID-19 critical illness course, which is becoming more prevalent.

Local and Intra-articular Administration of Nonsteroidal Anti-inflammatory Drugs for Pain Management in Orthopedic Surgery.

BACKGROUND: Although growing evidence demonstrates the benefits of locally administered nonsteroidal anti-inflammatory drugs (NSAIDs) for postoperative pain management, there is ongoing debate regarding NSAID use in orthopedic surgery. AREAS OF UNCERTAINTY: Current data largely support a local site of NSAID action and suggest that effective pain control can be achieved with delivery of NSAIDs intra-articularly (IA) and/or locally at the site of injury, where they can block peripheral production of inflammatory mediators and may desensitize nociceptors. Improvements in postoperative pain control with locally administered NSAIDs have been widely reported in the total joint arthroplasty literature and may offer benefits in patient's undergoing arthroscopic procedures and those with osteoarthritis as well. The purpose of this review is to examine the available evidence in the literature regarding the efficacy and safety profile of the use of local and IA NSAIDs in orthopedic surgery. DATA SOURCES: Narrative literature review using keywords, expert opinion, either during or from live conference. THERAPEUTIC ADVANCES: Local and IA administration of NSAIDs for pain management in orthopedic surgery. CONCLUSION: There is convincing evidence that NSAIDs administered locally in and around the joint reduce postoperative pain scores and opioid consumption in patients undergoing total joint arthroplasty, yet further research is required regarding the risks of potential chondrotoxicity and the inhibition of bone and soft-tissue healing with locally administered NSAIDs.

The Effect of Increased Intraocular Pressure During Steep Trendelenburg Positioning in Robotic Prostatectomy and Hysterectomy on Structural and Functional Ocular Parameters.

BACKGROUND: Robotic prostatectomy and robotic hysterectomy require steep Trendelenburg positioning. Many authors documented significant increases in intraocular pressure (IOP) during steep Trendelenburg. However, the long-term biological effect of a significant increase in IOP on the structural and functional ocular system is unknown. This study examines the effect of a significant increase in IOP on the visual acuity, retinal nerve fiber layer thickness (RNFLT), and ganglion cell complex (GCC) thickness in 52 patients without preexisting ocular disease of both genders before and 3 months after their procedures. METHODS: This was a prospective cohort study. The total number of patients included was 56, then 3 females and 1 male case were excluded, totaling 28 robotic hysterectomies and 24 robotic prostatectomies were performed. Patients underwent complete eye examination before the procedure and 3 months after, measuring the main outcome of RNFLT and the secondary outcomes of GCC thickness, foveal threshold (FT), mean deviation (MD), and pattern standard deviation (PSD). These outcomes were analyzed using linear mixed-effects models. On the day of surgery, we examined the IOP after induction of anesthesia, at the end of steep Trendelenburg, and in the recovery room. RESULTS: There were significant differences in IOP values at the end of steep Trendelenburg versus after induction and 45-60 minutes post-awakening (P < .001 for both groups). No difference between IOP 45 and 60 minutes post-awakening and IOP after induction was observed in either group. The highest IOPs occurred at the end of the steep Trendelenburg time point for both groups. The mean duration of steep Trendelenburg in robotic prostatectomy was 184.6 minutes (standard deviation [SD] = 30.8), while the mean duration in robotic hysterectomy was 123.0 minutes (SD = 29.8). All ophthalmologic examinations were normal preoperatively and 3 months postoperatively. The ocular parameters in the retina and optic disk did not differ significantly before surgery and 3 months after. CONCLUSIONS: There is a significant increase in IOP during steep Trendelenburg positioning. There was no significant difference in the ocular parameters examined 3 months after the procedure in this cohort.

Prediction of Opioid-Induced Respiratory Depression on Inpatient Wards Using Continuous Capnography and Oximetry: An International Prospective, Observational Trial.

BACKGROUND: Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring. METHODS: PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and Asia. Vital signs were intermittently monitored per standard of care. A total of 1335 patients receiving parenteral opioids and continuously monitored on the general care floor were included in the analysis. A respiratory depression episode was defined as respiratory rate ≤5 breaths/min (bpm), oxygen saturation ≤85%, or end-tidal carbon dioxide ≤15 or ≥60 mm Hg for ≥3 minutes; apnea episode lasting >30 seconds; or any respiratory opioid-related adverse event. A risk prediction tool was derived using a multivariable logistic regression model of 46 a priori defined risk factors with stepwise selection and was internally validated by bootstrapping. RESULTS: One or more respiratory depression episodes were detected in 614 (46%) of 1335 general care floor patients (43% male; mean age, 58 ± 14 years) continuously monitored for a median of 24 hours (interquartile range [IQR], 17-26). A multivariable respiratory depression prediction model with area under the curve of 0.740 was developed using 5 independent variables: age ≥60 (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. The PRODIGY risk prediction tool showed significant separation between patients with and without respiratory depression (P < .001) and an odds ratio of 6.07 (95% confidence interval [CI], 4.44-8.30; P < .001) between the high- and low-risk groups. Compared to patients without respiratory depression episodes, mean hospital length of stay was 3 days longer in patients with ≥1 respiratory depression episode (10.5 ± 10.8 vs 7.7 ± 7.8 days; P < .0001) identified using continuous oximetry and capnography monitoring. CONCLUSIONS: A PRODIGY risk prediction model, derived from continuous oximetry and capnography, accurately predicts respiratory depression episodes in patients receiving opioids on the general care floor. Implementation of the PRODIGY score to determine the need for continuous monitoring may be a first step to reduce the incidence and consequences of respiratory compromise in patients receiving opioids on the general care floor.

Amisulpride for the Rescue Treatment of Postoperative Nausea or Vomiting in Patients Failing Prophylaxis: A Randomized, Placebo-controlled Phase III Trial.

BACKGROUND: Although antiemetics are commonly used to prevent postoperative nausea or vomiting, the failure rate is appreciable and there is currently no generally accepted standard for rescue treatment of postoperative nausea or vomiting after failed prophylaxis. This prospective, randomized, double-blind, parallel-group, placebo-controlled, multicenter study was designed to test the hypothesis that intravenous amisulpride, a dopamine D2/D3-antagonist, is superior to placebo at treating established postoperative nausea or vomiting after failed prophylaxis. METHODS: A total of 2,285 adult patients undergoing surgery under general inhalational anesthesia and receiving standard antiemetic prophylaxis were enrolled at 23 sites in Canada, France, Germany, and the United States. Of these, 702 patients experienced postoperative nausea or vomiting in the 24-h period after surgery and were randomized to receive a single dose of 5 or 10 mg intravenous amisulpride or matching placebo. The primary endpoint was complete response, defined as no emesis or rescue antiemetic use for 24 h after study drug administration, excluding emesis in the first 30 min. Secondary endpoints included incidence of emesis and rescue medication use, nausea burden, time to treatment failure, and length of stay in postanesthesia care unit and hospital. RESULTS: Complete response occurred in significantly more patients receiving 10 mg amisulpride (96 of 230, 41.7%) than placebo (67 of 235, 28.5%), a 13.2% difference (95% CI, 4.6 to 21.8; odds ratio, 1.80; P = 0.006). A 5-mg dose of amisulpride did not show a significant benefit (80 of 237, 33.8%); the difference from placebo was 5.2% (95% CI, 3.1 to 13.6; odds ratio, 1.24; P = 0.109). The total number of adverse events recorded and proportion of patients with at least one adverse event were comparable between the placebo and amisulpride groups. No clinically relevant toxicities were observed. CONCLUSIONS: A single 10-mg dose of intravenous amisulpride was safe and more effective than placebo at treating established postoperative nausea or vomiting in patients failing postoperative nausea or vomiting prophylaxis.

Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Amisulpride as Treatment of Established Postoperative Nausea and Vomiting in Patients Who Have Had No Prior Prophylaxis.

BACKGROUND: Postoperative nausea and vomiting (PONV) occurs commonly in surgical patients despite widespread prophylactic antiemetic use. Rescue options are currently limited. 5HT3 antagonists are most frequently used for prophylaxis, but if they fail, additional doses are not effective as rescue medication. Intravenous (IV) amisulpride, a well-studied D2/D3 antagonist, has been shown in trials to prevent PONV. This study was designed to determine if amisulpride could be used to treat established PONV in patients at low-to-moderate risk of PONV who had not received any prior prophylaxis. METHODS: Men and women aged over 18 years were permitted to enroll if they were to undergo general inhalational anesthesia, expected to last at least 1 hour, for an outpatient or inpatient surgical procedure. Patients who then suffered PONV were randomized equally to 1 of 3 single-dose IV regimens: placebo or 5 or 10 mg amisulpride. The primary end point was complete response, defined as no emesis in the period 30 minutes to 24 hours after study drug treatment and no use of rescue medication in the entire 24-hour period. RESULTS: One thousand nine hundred eighty-eight patients were enrolled preoperatively, of whom 560 were randomized to a treatment arm. Complete response occurred in 39 of 181 patients (21.5%) in the placebo group compared to 60 of 191 patients (31.4%; P = .016) and 59 of 188 patients (31.4%; P = .016) in the amisulpride 5 and 10 mg groups, respectively. The adverse event profile of amisulpride at either dose was similar to placebo. CONCLUSIONS: IV amisulpride at 5 and 10 mg was safe and efficacious in the treatment of established PONV in surgical patients undergoing general anesthesia with no prior PONV prophylaxis.

Amisulpride Prevents Postoperative Nausea and Vomiting in Patients at High Risk: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated. METHODS: This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors. Patients were randomized to receive either intravenous amisulpride (5 mg) or matching placebo at induction of general anesthesia, in addition to one standard, nondopaminergic antiemetic, most commonly ondansetron or dexamethasone. Vomiting/retching, nausea, and use of rescue medication were recorded for 24 h after wound closure. The primary endpoint was complete response, defined as no emesis or rescue medication use in the 24-h postoperative period. RESULTS: Complete response occurred in 330 of 572 (57.7%) of the amisulpride group and 268 of 575 (46.6%) of the control group (difference 11.1 percentage points; 95% CI, 5.3 to 16.8; P < 0.001). The incidences of emesis (13.8% vs. 20.0%, P = 0.003), any nausea (50.0% vs. 58.3%, P = 0.002), significant nausea (37.1% vs. 47.7%, P < 0.001), and rescue medication use (40.9% vs. 49.4%, P = 0.002) were significantly lower in the amisulpride group. Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently with amisulpride than with placebo. CONCLUSIONS: Intravenous amisulpride was safe and effective as prophylaxis of postoperative nausea and vomiting when given in combination with an antiemetic from another class to adult patients at high risk for suffering postoperative nausea and vomiting undergoing elective surgery under inhalational general anesthesia. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B727.

Current Perspective on the Use of Opioids in Perioperative Medicine: An Evidence-Based Literature Review, National Survey of 70,000 Physicians, and Multidisciplinary Clinical Appraisal.

Objective: Opioids represent an important analgesic option for physicians managing acute pain in surgical patients. Opioid management is not without its drawbacks, however, and current trends suggest that opioids might be overused in the United States. An expert panel was convened to conduct a clinical appraisal regarding the use of opioids in the perioperative setting. Methods: The clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the statement "Opioids are not overused in the United States, even though opioid adjunct therapy achieves greater pain control with less risk." The authors' evaluation of this statement was also compared with the results of a national survey of surgeons and anesthesiologists in the United States. Results: We report the presented literature and proceedings of the panel discussion. The national survey revealed a wide range of opinions regarding opioid overuse in the United States. Current published evidence provides support for the efficacy of opioid therapy in surgical patients; however, it is not sufficient to conclude unequivocally that opioids are-or are not-overused in the management of acute surgical pain in the United States. Conclusions: Opioids remain a key component of multimodal perioperative analgesia, and strategic opioid use based on clinical considerations and patient-specific needs represents an opportunity to support improved postoperative outcomes and satisfaction. Future studies should focus on identifying optimal procedure-specific and patient-centered approaches to multimodal perioperative analgesia.

Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting: Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials.

BACKGROUND: Two essentially identical, randomized, double-blind, placebo-controlled, parallel-group phase III studies evaluated the efficacy of intravenous amisulpride, a dopamine D2/D3 antagonist, in the prevention of postoperative nausea and vomiting in adult surgical patients. METHODS: Adult inpatients undergoing elective surgery during general anesthesia and having at least two of the four Apfel risk factors for postoperative nausea and vomiting were enrolled at 9 U.S. and 10 European sites. A single 5-mg dose of amisulpride or matching placebo was given at induction of anesthesia. The primary endpoint was complete response, defined as no vomiting/retching and no use of antiemetic rescue medication in the 24-h postoperative period. Nausea incidence was a secondary endpoint. RESULTS: Across the two studies, 689 patients were randomized and dosed with study medication, of whom 626 were evaluable per protocol. In the U.S. study, 46.9% (95% CI, 39.0 to 54.9) of patients achieved complete response in the amisulpride group compared to 33.8% (95% CI, 26.2 to 42.0) in the placebo group (P = 0.026). In the European study, complete response rates were 57.4% (95% CI, 49.2 to 65.3) for amisulpride and 46.6% (95% CI, 38.8 to 54.6) for placebo (P = 0.070). Nausea occurred less often in patients who received amisulpride than those who received placebo. There was no clinically significant difference in the safety profile of amisulpride and placebo; in particular, there were no differences in terms of QT prolongation, extrapyramidal side effects, or sedation. CONCLUSIONS: One of the two trials demonstrated superiority, while pooling both in a post hoc change to the plan of analysis supported the hypothesis that amisulpride was safe and superior to placebo in reducing the incidence of postoperative nausea and vomiting in a population of adult inpatients at moderate to high risk of postoperative nausea and vomiting.

Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender.

BACKGROUND: Clopidogrel is an irreversible antagonist of P2Y12 receptors (P2Y12Rs) used as an antiplatelet drug to reduce risk of thrombosis. P2Y12Rs are expressed in gastrointestinal (GI) tract where they might regulate GI function. AIM: To evaluate if blockade of P2Y12Rs by clopidogrel is associated with higher incidence of GI symptoms in patients with irritable bowel syndrome (IBS). METHODS: A retrospective analysis of our institutional database was conducted for a 13-year period. IBS patients were identified, and their demographics, GI symptoms and clopidogrel therapy were collected. Logistic regression models were used to characterize symptoms in clopidogrel versus no-clopidogrel IBS-groups, adjusting for Age and Sex differences. An additional study characterized the P2Y12R distribution in human gut. RESULTS: The search identified 7217 IBS patients (6761 no-clopidogrel/456 clopidogrel). There were a higher proportion of patients with GI symptoms on clopidogrel (68%) compared to controls (60%, p = 0.0011) that were Females (70 vs. 60%, p = 0.0003) not Males (61 vs. 60%; p = 0.8312). In Females, clopidogrel was associated with higher incidence of GI symptoms (Age adjusted; p < 0.0001) for pain, constipation, gastroparesis (p ≤ 0.0001) and psychogenic pain (p = 0.0006). Age or Sex (adjusted models) influenced one or more GI symptoms (i.e., pain, p < 0.0001; constipation, p < 0.0001/p = 0.008; diarrhea, flatulence, p = 0.01). P2Y12R immunoreactivity was abundant in human ENS; glial-to-neuron ratio of P2Y12Rs expressed in Females â‰« Males. CONCLUSIONS: Irreversible blockade of P2Y12R by clopidogrel is associated with higher incidence of GI symptoms in Female IBS patients, although Age or Sex alone contributes to symptomatology. Prospective studies can determine clinical implications of P2Y12Rs in IBS.

Multicenter Study Validating Accuracy of a Continuous Respiratory Rate Measurement Derived From Pulse Oximetry: A Comparison With Capnography.

BACKGROUND: Intermittent measurement of respiratory rate via observation is routine in many patient care settings. This approach has several inherent limitations that diminish the clinical utility of these measurements because it is intermittent, susceptible to human error, and requires clinical resources. As an alternative, a software application that derives continuous respiratory rate measurement from a standard pulse oximeter has been developed. We sought to determine the performance characteristics of this new technology by comparison with clinician-reviewed capnography waveforms in both healthy subjects and hospitalized patients in a low-acuity care setting. METHODS: Two independent observational studies were conducted to validate the performance of the Medtronic Nellcor Respiration Rate Software application. One study enrolled 26 healthy volunteer subjects in a clinical laboratory, and a second multicenter study enrolled 53 hospitalized patients. During a 30-minute study period taking place while participants were breathing spontaneously, pulse oximeter and nasal/oral capnography waveforms were collected. Pulse oximeter waveforms were processed to determine respiratory rate via the Medtronic Nellcor Respiration Rate Software. Capnography waveforms reviewed by a clinician were used to determine the reference respiratory rate. RESULTS: A total of 23,243 paired observations between the pulse oximeter-derived respiratory rate and the capnography reference method were collected and examined. The mean reference-based respiratory rate was 15.3 ± 4.3 breaths per minute with a range of 4 to 34 breaths per minute. The Pearson correlation coefficient between the Medtronic Nellcor Respiration Rate Software values and the capnography reference respiratory rate is reported as a linear correlation, R, as 0.92 ± 0.02 (P < .001), whereas Lin's concordance correlation coefficient indicates an overall agreement of 0.85 ± 0.04 (95% confidence interval [CI] +0.76; +0.93) (healthy volunteers: 0.94 ± 0.02 [95% CI +0.91; +0.97]; hospitalized patients: 0.80 ± 0.06 [95% CI +0.68; +0.92]). The mean bias of the Medtronic Nellcor Respiration Rate Software was 0.18 breaths per minute with a precision (SD) of 1.65 breaths per minute (healthy volunteers: 0.37 ± 0.78 [95% limits of agreement: -1.16; +1.90] breaths per minute; hospitalized patients: 0.07 ± 1.99 [95% limits of agreement: -3.84; +3.97] breaths per minute). The root mean square deviation was 1.35 breaths per minute (healthy volunteers: 0.81; hospitalized patients: 1.60). CONCLUSIONS: These data demonstrate the performance of the Medtronic Nellcor Respiration Rate Software in healthy subjects and patients hospitalized in a low-acuity care setting when compared with clinician-reviewed capnography. The observed performance of this technology suggests that it may be a useful adjunct to continuous pulse oximetry monitoring by providing continuous respiratory rate measurements. The potential patient safety benefit of using combined continuous pulse oximetry and respiratory rate monitoring warrants assessment.

Non-opioid anesthetic drug abuse among anesthesia care providers: a narrative review.

PURPOSE: The objective of this narrative review is to provide an overview of the problem of non-opioid anesthetic drug abuse among anesthesia care providers (ACPs) and to describe current approaches to screening, therapy, and rehabilitation of ACPs suffering from non-opioid anesthetic drug abuse. SOURCE: We first performed a search of all literature available on PubMed prior to April 11, 2016. The search was limited to articles published in Spanish and English, and the following key words were used: anesthesiology, anesthesia personnel, AND substance-related disorders. We also searched Ovid MEDLINE® databases from 1946-April 11, 2016 using the following search terms: anesthesiology OR anesthesia, OR nurse anesthetist OR anesthesia care provider OR perioperative nursing AND substance-related disorders. PRINCIPAL FINDINGS: Despite an increased awareness of drug abuse among ACPs and improvements in preventive measures, the problem of non-opioid anesthetic drug abuse remains significant. While opioids are the most commonly abused anesthesia medications among ACPs, the abuse of non-opioid anesthetics is a significant cause of morbidity, mortality, and professional demise. CONCLUSION: Early detection, effective therapy, and long-term follow-up help ACPs cope more effectively with the problem and, when possible, resume their professional activities. There is insufficient evidence to determine the ability of ACPs to return safely to anesthesia practice after rehabilitation, though awareness of the issue and ongoing treatment are necessary to minimize patient risk from potentially related clinical errors.

Perioperative Aspirin for Prevention of Venous Thromboembolism: The PeriOperative ISchemia Evaluation-2 Trial and a Pooled Analysis of the Randomized Trials.

BACKGROUND: The PeriOperative ISchemia Evaluation-2 (POISE-2) trial compared aspirin with placebo after noncardiac surgery. METHODS: The authors randomly assigned 10,010 patients undergoing noncardiac surgery to receive 200 mg aspirin or placebo 2 to 4 h before surgery and then 100 mg aspirin daily or placebo daily for up to 30 days after surgery. Herein, the authors report the effect of aspirin on venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, as well as an updated pooled analysis of randomized trials of antiplatelet therapy for VTE prevention in noncardiac surgery patients. RESULTS: Six thousand five hundred forty-eight patients (65.4%) received anticoagulant prophylaxis. VTE occurred in 53 patients (1.1%) allocated to aspirin and in 60 patients (1.2%) allocated to placebo (hazard ratio, 0.89; 95% CI, 0.61 to 1.28). Major or life-threatening bleeding occurred in 312 patients (6.3%) allocated to aspirin and in 256 patients (5.1%) allocated to placebo (hazard ratio, 1.22; 95% CI, 1.04 to 1.44). Concomitant use of anticoagulant prophylaxis did not modify the effect of aspirin on VTE or bleeding. Pooled analysis of the POISE-2 and Pulmonary Embolism Prevention trials demonstrated that symptomatic VTE occurred in 173 (1.3%) of 13,724 patients allocated to aspirin and in 246 (1.8%) of 13,730 patients allocated to placebo (odds ratio, 0.71; 95% CI, 0.56 to 0.89; heterogeneity P = 0.27; I = 17%); the impact of aspirin was very similar in those who did and did not receive pharmacologic prophylaxis. Pooled estimates for symptomatic VTE were similar to the pooled estimates for any deep vein thrombosis and pulmonary embolism from the POISE-2 trial, Pulmonary Embolism Prevention trial, and the Antiplatelet Trialists' Collaboration meta-analysis. CONCLUSIONS: Aspirin in the POISE-2 trial did not reduce VTE, but two thirds of patients received anticoagulant prophylaxis, there were few VTE events, and results were consistent with a wide range of aspirin effects. A pooled analysis of the randomized trials demonstrates evidence for the efficacy of aspirin for VTE prevention in hospitalized surgical patients.

A Prospective, Comparative Study for the Evaluation of Postoperative Pain and Quality of Recovery in Patients Undergoing Robotic Versus Open Hysterectomy for Staging of Endometrial Cancer.

STUDY OBJECTIVE: To measure and compare postoperative pain and patient satisfaction in patients undergoing either robotic or open laparotomy for surgical staging of endometrial cancer. DESIGN: Prospective, comparative study (Canadian Task Force classification II). SETTING: University hospital. PATIENTS: A total of 142 patients undergoing either robotic or open laparotomy for surgical staging of endometrial cancer. INTERVENTIONS: Patients scheduled for surgical staging of endometrial cancer at a single institution were identified. The patients underwent either robotic or open hysterectomy for staging of endometrial cancer. The choice of operative approach (robotic vs laparotomy) was made by the faculty physician before enrollment. Patients participated in the study for up to 48 hours for pain assessments and up to 10 ± 3 days postoperatively for quality of recovery assessments. MEASUREMENTS AND MAIN RESULTS: The following measurements were performed: postoperative pain with the visual analog scale (VAS), 24-hour opioid consumption, and quality of recovery using the Quality of Recovery Questionnaire (QoR-40). The study was terminated owing to futility, given the lack of open procedures at our institution. Despite that lack of statistically significant difference between VAS scores at rest and with leg extension, there was a significant decrease in 24-hour opioid consumption in the robotic group. In addition, the QoR-40 showed an increased perception of recovery in patients within the robotic group compared with the laparotomy group. CONCLUSION: Patients with endometrial cancer who underwent robotic surgery had decreased postoperative opioid consumption and improved quality of recovery compared with those who underwent surgery via laparotomy.