Pain management, fluid therapy and thromboprophylaxis after pancreatoduodenectomy: a worldwide survey among surgeons.

BACKGROUND: The aim of this survey was to assess practices regarding pain management, fluid therapy and thromboprophylaxis in patients undergoing pancreatoduodenectomy on a global basis. METHODS: This survey study among surgeons from eight (inter)national scientific societies was performed according to the CHERRIES guideline. RESULTS: Overall, 236 surgeons completed the survey. ERAS protocols are used by 61% of surgeons and respectively 82%, 93%, 57% believed there is a relationship between pain management, fluid therapy, and thromboprophylaxis and clinical outcomes. Epidural analgesia (50%) was most popular followed by intravenous morphine (24%). A restrictive fluid therapy was used by 58% of surgeons. Chemical thromboprophylaxis was used by 88% of surgeons. Variations were observed between continents, most interesting being the choice for analgesic technique (transversus abdominis plane block was popular in North America), restrictive fluid therapy (little use in Asia and Oceania) and duration of chemical thromboprophylaxis (large variation). CONCLUSION: The results of this international survey showed that only 61% of surgeons practice ERAS protocols. Although the majority of surgeons presume a relationship between pain management, fluid therapy and thromboprophylaxis and clinical outcomes, variations in practices were observed. Additional studies are needed to further optimize, standardize and implement ERAS protocols after pancreatic surgery.

Does nociception monitor-guided anesthesia affect opioid consumption? A systematic review of randomized controlled trials.

Monitors that estimate nociception during anesthesia may be used to guide opioid and other analgesics administration to optimize anesthesia care and possibly outcome. We reviewed the literature to evaluate current evidence of the effect of nociception-guided management over standard anesthesia practice during surgery. A systematic review of the literature on the effect of nociception monitoring on anesthesia practice was conducted. Reports were eligible if they compared nociception-guided anesthesia to standard practice during surgery. Primary endpoint of this review is intraoperative opioid consumption. Secondary endpoints included hemodynamic control, postoperative pain and pain treatment. We identified 12 randomized controlled trials that compared one of five different nociception monitoring techniques to standard anesthesia care. Most studies were single center studies of small sample size. Six studies reported intraoperative opioid consumption as primary outcome. There was considerable variability with respect to surgical procedure and anesthesia technique. For nociception monitors that were investigated by more than one study, analysis of the pooled data was performed. The surgical plethysmographic index was the only monitor for which an intra operative opioid sparing effect was found. For the other monitors, either no effect was detected, or pooled analysis could not be performed due to paucity of study data. On secondary outcomes, no consistent effect of nociception-guided anesthesia could be established. Although some nociception monitors show promising results, no definitive conclusions regarding the effect of nociception monitoring on intraoperative opioid consumption or other anesthesia related outcome can be drawn.Clinical trial number PROSPERO ID 102913.

Nociception-guided versus Standard Care during Remifentanil-Propofol Anesthesia: A Randomized Controlled Trial.

BACKGROUND: The multidimensional index of nociception, the nociception level, outperforms blood pressure and heart rate in detection of nociceptive events during anesthesia. We hypothesized that nociception level-guided analgesia reduces opioid consumption and suboptimal anesthesia events such as low blood pressure and use of vasoactive medication. METHODS: In this single-blinded randomized study, 80 American Society of Anesthesiologists class I-III adult patients of either sex, scheduled for major abdominal procedures under remifentanil/propofol anesthesia by target-controlled infusion, were included. During the procedure nociception level, noninvasive blood pressure, and heart rate were monitored. Patients were randomized to receive standard clinical care or nociception level-guided analgesia. In the nociception level-guided group, remifentanil concentration was reduced when index values were less than 10 or increased when values were above 25 for at least 1 min, in steps of 0.5 to 1.0 ng/ml. Propofol was titrated to bispectral index values between 45 and 55. The primary outcomes of the study were remifentanil and propofol consumption and inadequate anesthesia events. RESULTS: Compared with standard care, remifentanil administration was reduced in nociception level-guided patients from (mean ± SD) 0.119 ± 0.033 to 0.086 ± 0.032 µg · kg · min (mean difference, 0.039 µg · kg · min; 95% CI, 0.025-0.052 µg · kg · min; P < 0.001). Among nociception level-guided patients, 2 of 40 (5%) experienced a hypotensive event (mean arterial pressure values less than 55 mm Hg) versus 11 of 40 (28%) patients in the control group (relative risk, 0.271; 95% CI, 0.08-0.77; P = 0.006). In the nociception level-guided group, 16 of 40 (40%) patients received vasoactive medication versus 25 of 40 (63%) patients in the standard care group (relative risk, 0.64; 95% CI, 0.40-0.99; P = 0.044). CONCLUSIONS: Nociception level-guided analgesia during major abdominal surgery resulted in 30% less remifentanil consumption.

Reversal of Partial Neuromuscular Block and the Ventilatory Response to Hypoxia: A Randomized Controlled Trial in Healthy Volunteers.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The ventilatory response to hypoxia is a critical reflex that is impaired by neuromuscular blocking drugs. However, the degree to which this reflex is restored after reversal of blockade is unknown. WHAT THIS ARTICLE TELLS US THAT IS NEW: Despite full reversal of neuromuscular blockade at the thumb using different drug classes, this hypoxic chemoreflex is not fully restored. BACKGROUND: The ventilatory response to hypoxia is a life-saving chemoreflex originating at the carotid bodies that is impaired by nondepolarizing neuromuscular blocking agents. This study evaluated the effect of three strategies for reversal of a partial neuromuscular block on ventilatory control in 34 healthy male volunteers on the chemoreflex. The hypothesis was that the hypoxic ventilatory response is fully restored following the return to a train-of-four ratio of 1. METHODS: In this single-center, experimental, randomized, controlled trial, ventilatory responses to 5-min hypoxia (oxygen saturation, 80 ± 2%) and ventilation at hyperoxic isohypercapnia (end-tidal carbon dioxide concentration, 55 mmHg) were obtained at baseline, during rocuronium-induced partial neuromuscular block (train-of-four ratio of 0.7 measured at the adductor pollicis muscle by electromyography), and following reversal until the train-of-four ratio reached unity with placebo (n = 12), 1 mg neostigmine/0.5 mg atropine (n = 11), or 2 mg/kg sugammadex (n = 11). RESULTS: This study confirmed that low-dose rocuronium reduced the ventilatory response to hypoxia from 0.55 ± 0.22 (baseline) to 0.31 ± 0.21 l · min · % (train-of-four ratio, 0.7; P < 0.001). Following full reversal as measured at the thumb, there was persistent residual blunting of the hypoxic ventilatory response (0.45 ± 0.16 l · min · %; train-of-four ratio, 1.0; P < 0.001). Treatment effect was not significant (analysis of covariance, P = 0.299) with chemoreflex impairment in 5 (45%) subjects following sugammadex reversal, in 7 subjects (64%) following neostigmine reversal, and in 10 subjects (83%) after spontaneous reversal to a train-of-four ratio of 1. CONCLUSIONS: Despite full reversal of partial neuromuscular block at the thumb, impairment of the peripheral chemoreflex may persist at train-of-four ratios greater than 0.9 following reversal with neostigmine and sugammadex or spontaneous recovery of the neuromuscular block.

Efficacy of profound versus moderate neuromuscular blockade in enhancing postoperative recovery after laparoscopic donor nephrectomy: A randomised controlled trial.

BACKGROUND: Profound neuromuscular blockade (NMB) during anaesthesia has been shown to reduce postoperative pain scores, when compared with a moderate block. We hypothesised that profound NMB during laparoscopic donor nephrectomy (LDN) could also improve the early quality of recovery after surgery. OBJECTIVES: To compare the effectiveness of profound versus moderate NMB during LDN in enhancing postoperative recovery. DESIGN: A phase IV, double-blinded, randomised controlled trial. SETTING: Multicentre trial, from November 2016 to December 2017. PATIENTS: A total of 101 living kidney donors scheduled for LDN were enrolled, and 96 patients were included in the analyses. INTERVENTIONS: Patients were randomised to receive profound (posttetanic count 1 to 3) or moderate (train-of-four count 1 to 3) neuromuscular block. MAIN OUTCOME MEASURES: The primary outcome was the early quality of recovery at postoperative day 1, measured by the Quality of Recovery-40 Questionnaire. Secondary outcomes were adverse events, postoperative pain, analgesic consumption and length-of-stay. RESULTS: The intention-to-treat analysis did not show a difference with regard to the quality of recovery, pain scores, analgesic consumption and length-of-stay. Less intra-operative adverse events occurred in patients allocated to profound NMB (1/48 versus 6/48). Five patients allocated to a profound NMB received a moderate block and in two patients neuromuscular monitoring failed. The as-treated analysis revealed that pain scores were significantly lower at 6, 24 and 48 h after surgery. Moreover, the quality of recovery was significantly better at postoperative day 2 in patients receiving a profound versus moderate block (179.5 ±â€Š13.6 versus 172.3 ±â€Š19.2). CONCLUSION: Secondary analysis indicates that an adequately maintained profound neuromuscular block improves postoperative pain scores and quality of recovery. As the intention-to-treat analysis did not reveal a difference regarding the primary endpoint, future studies should pursue whether a thoroughly maintained profound NMB during laparoscopy improves relevant patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02838134.

Ability of the nociception level, a multiparameter composite of autonomic signals, to detect noxious stimuli during propofol-remifentanil anesthesia.

BACKGROUND: A novel multidimensional index of nociception, the nociception level (NoL) index, derived from the nonlinear composite of heart rate (HR), HR variability, amplitude of the photoplethysmogram, skin conductance, fluctuations in skin conductance, and their time derivatives, was used to assess nociception during anesthesia. METHODS: Seventy-two American Society of Anesthesiologists I to III patients received propofol (target bispectral index, 45) and one of six remifentanil target concentrations in the range of 0 to 5 ng/ml. The NoL, mean arterial pressure (MAP; derived from a beat-to-beat finger cuff measurement), and HR were measured during nonnoxious, moderate noxious (skin incision), and intense noxious (intubation) stimulation. Values are represented as average (95% CI). RESULTS: NoL, HR, and MAP did not change during nonnoxious events. Incision increased HR by 1.3/min (-0.46 to 3.1/min; not significant), MAP by 7.9 mmHg (-1.9 to 13.0 mmHg; not significant), and NoL by 8.0 (0.4 to 16.0; P < 0.001). Intubation increased HR by 7.0/min (1.4 to 12.0/min; P < 0.001), MAP by 13.0 mmHg (3.1 to 20 mmHg; P < 0.001), and NoL by 18.0 (7.8 to 29.0; P < 0.001). The ΔNoL area under the curve (0.95) of the receiver operating characteristic curve was greater compared with ΔHR (0.84, P < 0.001) and ΔMAP (0.78, P < 0.001). Under nonnociceptive conditions, remifentanil had no effect on NoL, in contrast to HR and MAP that showed a dose-dependent decrease. CONCLUSIONS: The NoL is a reliable measure of moderate and intense noxious stimulation and outperforms HR and MAP in differentiating noxious from nonnoxious stimuli. In contrast to HR and MAP, the NoL was not affected by hemodynamic effects of remifentanil.

The Use of Muscle Relaxants and Reversal Agents in a Setting Without Cost Restrictions: Experience from a Tertiary Academic Hospital in the Netherlands.

Introduction: Muscle relaxants are often given during general anesthesia to facilitate endotracheal intubation. However lingering effects after anesthesia-end may lead to respiratory compromise in the PACU. Strategies to reduce these adverse events include monitoring neuromuscular block, the use of short-acting agents and active pharmacological reversal before extubation. At Leiden University Medical Center (LUMC), a tertiary care academic hospital in the Netherlands, various muscle relaxants and reversal agents are freely available to all clinicians without restrictions. In this setting, we intended to evaluate how patient and surgical characteristics impacted the use of these agents for a variety of non-cardiac surgeries. Material and Methods: This is a retrospective database study of adult patients that had received elective, non-cardiac surgery and general anesthesia with endotracheal intubation between 2016 and 2020 at LUMC in the Netherlands. Exclusion criteria consisted of patients pharmacologically reversed with both sugammadex and neostigmine during the same procedure, diagnosed with myasthenia gravis, receiving pyridostigmine therapy, or with renal failure (eGFR <30 mL.min.1.73m2). Results: We retrieved 23,373 patient records of which 9742 were excluded because one or more exclusion criteria were met. The final cohort consisted of 13,631 cases. Rocuronium was the most commonly used muscle relaxant (88.5%); sugammadex was the most commonly used reversal agent (99.9% of those pharmacologically reversed). Of all cases that received rocuronium as muscle relaxant, 76.9% of patients were not reversed, while 23.1% were reversed with sugammadex. The odds of reversal increased with age, BMI, ASA class (1-3) and shorter duration of surgery. Conclusion: In an unrestricted clinical environment, rocuronium and sugammadex are the preferred agents for muscle relaxation and reversal. Pharmacologic reversal of neuromuscular block was uncommon overall, but more likely in older and obese patients, higher ASA classification and shorter lasting procedures. Sugammadex has largely replaced neostigmine for this purpose.

Deep neuromuscular block reduces the incidence of intra-operative complications during laparoscopic donor nephrectomy: a pooled analysis of randomized controlled trials.

STUDY OBJECTIVE: To assess whether different intensities of intra-abdominal pressure and deep neuromuscular blockade influence the risk of intra-operative surgical complications during laparoscopic donor nephrectomy. DESIGN: A pooled analysis of ten previously performed prospective randomized controlled trials. SETTING: Laparoscopic donor nephrectomy performed in four academic hospitals in the Netherlands: Radboudumc, Leiden UMC, Erasmus MC Rotterdam, and Amsterdam UMC. PATIENTS: Five hundred fifty-six patients undergoing a transperitoneal, fully laparoscopic donor nephrectomy enrolled in ten prospective, randomized controlled trials conducted in the Netherlands from 2001 to 2017. INTERVENTIONS: Moderate (tetanic count of four > 1) versus deep (post-tetanic count 1-5) neuromuscular blockade and standard (≥10 mmHg) versus low (<10 mmHg) intra-abdominal pressure. MEASUREMENTS: The primary endpoint is the number of intra-operative surgical complications defined as any deviation from the ideal intra-operative course occurring between skin incision and closure with five severity grades, according to ClassIntra. Multiple logistic regression analyses were used to identify predictors of intra- and postoperative complications. MAIN RESULTS: In 53/556 (9.5%) patients, an intra-operative complication with ClassIntra grade ≥ 2 occurred. Multiple logistic regression analyses showed standard intra-abdominal pressure (OR 0.318, 95% CI 0.118-0.862; p = 0.024) as a predictor of less intra-operative complications and moderate neuromuscular blockade (OR 3.518, 95% CI 1.244-9.948; p = 0.018) as a predictor of more intra-operative complications. Postoperative complications occurred in 31/556 (6.8%), without significant predictors in multiple logistic regression analyses. CONCLUSIONS: Our data indicate that the use of deep neuromuscular blockade could increase safety during laparoscopic donor nephrectomy. Future randomized clinical trials should be performed to confirm this and to pursue whether it also applies to other types of laparoscopic surgery. TRIAL REGISTRATION: Clinicaltrials.gov LEOPARD-2 (NCT02146417), LEOPARD-3 trial (NCT02602964), and RELAX-1 study (NCT02838134), Klop et al. ( NTR 3096 ), Dols et al. 2014 ( NTR1433 ).

Early postoperative pain after laparoscopic donor nephrectomy predicts 30-day postoperative infectious complications: a pooled analysis of randomized controlled trials.

Our research group recently published a positive association between early postoperative pain and 30-day postoperative complications in a broad surgical population. To investigate whether heterogeneity of the population and surgical procedures influenced these results, we explored this association in a homogenous surgical population. A secondary analysis of the LEOPARD-2 (clinicaltrials.gov NCT02146417) and RELAX-1 study (NCT02838134) in laparoscopic donor nephrectomy patients (n = 160) was performed. Pain scores on the postanesthesia care unit and postoperative day (POD) 1 and 2 were compared between patients with infectious, noninfectious, and no complications 30 days after surgery. Patients who developed infectious complications had significantly higher pain scores on POD1 and 2 (6.7 ± 2.1 and 6.4 ± 2.8) than patients without complications (4.9 ± 2.2 and 4.1 ± 1.9), respectively (P = 0.006 and P = 0.000). Unacceptable pain (numeric rating scale [NRS] ≥ 6) on POD1 was reported by 72% of patients who developed infectious complications, compared to 38% with noninfectious complications and 30% without complications (P = 0.018). This difference was still present on POD2 at 67% with infectious complications, 21% with noninfectious, and 40% without complications (P = 0.000). Multiple regression analysis identified unacceptable pain (numeric rating scale ≥6) on POD2 as a significant predictor for 30-day infectious complications (odds ratio 6.09, P = 0.001). Results confirm the association between early postoperative pain and 30-day infectious complications in a separate, homogenous surgical population. Further clinical trials should focus on finetuning of postoperative analgesia to elucidate the effects on the endocrine and immune response, preserve immune homeostasis, and prevent postoperative infectious complications.

Epidural and Non-epidural Analgesia in Patients Undergoing Open Pancreatectomy: a Retrospective Cohort Study.

BACKGROUND: The use of epidural analgesia (EA) in pancreatic surgery remains under debate. This study compares patients treated with EA versus non-EA after open pancreatectomy in a tertiary referral center. METHODS: All patients undergoing open pancreatectomy from 2013 to 2017 were retrospectively reviewed. (Non-)EA was terminated on postoperative day (POD) 3 or earlier if required. RESULTS: In total, 190 (72.5%) patients received EA and 72 (27.5%) patients received non-EA (mostly intravenous morphine). EA was terminated prematurely in 32.6% of patients and non-EA in 10.5% of patients. Compared with non-EA patients, EA patients had significantly lower pain scores on POD 0 (1.10 (0-3.00) versus 3.00 (1.67-5.00), P < 0.001) and POD 1 (2.00 (0.50-3.41) versus 3.00 (2.00-3.80), P = 0.001), though significantly higher pain scores on POD 3 (3.00 (2.00-4.00) versus 2.33 (1.50-4.00), P < 0.001) and POD 4 (2.50 (1.50-3.67) versus 2.00 (0.50-3.00), P = 0.007). EA patients required more vasoactive medication perioperatively and had higher cumulative fluid balances on POD 1-3. Postoperative complications were similar between groups. CONCLUSIONS: In our cohort, patients with EA experienced significantly lower pain scores in the first PODs compared with non-EA, yet higher pain scores after EA had been terminated. Although EA patients required more vasoactive medication and fluid therapy, the complication rate was similar.

Deep Neuromuscular Block Improves Surgical Conditions during Bariatric Surgery and Reduces Postoperative Pain: A Randomized Double Blind Controlled Trial.

BACKGROUND: It remains unknown whether the administration of a deep neuromuscular block (NMB) during bariatric surgery improves surgical conditions and patient outcome. The authors studied the effect of deep versus moderate NMB in laparoscopic bariatric surgery on surgical conditions and postoperative pain. METHODS AND RESULTS: One hundred patients scheduled to undergo elective bariatric surgery were randomized to a deep NMB (post-tetanic-count 2-3) or a moderate NMB (train-of-four 1-2). The quality of the surgical field was scored using the Leiden-Surgical Rating Scale (L-SRS), a 5-point scale ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Three surgeons scored the L-SRS at 10-min intervals during surgery; postoperative pain scores were obtained in the postanesthesia-care-unit (PACU) and on the ward. Mean (95% confidence interval) L-SRS scores in moderate NMB 4.2 (4.0-4.4) versus 4.8 (4.7-4.9) in deep NMB (p < 0.001). Moderate NMB resulted in 17% of scores at L-SRS scores of 1-3, while deep NMB resulted in 100% scores at the high end of the L-SRS (4-5). Deep NMB led to improved pain scores in the PACU (4.6 (4.2-4.9) versus 3.9 (3.6-4.4), p = 0.03) and reduced shoulder pain on the ward (1.8 (1.5-2.1) versus 1.3 (1.1-1.5), p = 0.03). A composite score of pain and opioid use in the PACU favoured deep NMB (p = 0.001). CONCLUSIONS: In bariatric surgery, deep relaxation has advantages for surgeon and patient. Compared to moderate NMB, deep NMB produced stable and improved surgical conditions with less postoperative pain.