[New Approaches in Perioperative Algesimetry]. / Neue Ansätze in der perioperativen Algesimetrie.

The measurement of anaesthetic depth and muscle relaxation have been routine procedures during general anaesthesia for years. Quantification of intraoperative nociception, on the other hand, is still largely impossible. Various methods have been tested and commercialised for more than 10 years. However, a real breakthrough has not yet been achieved and the routine application of all methods available so far is not without problems. This article explains methodological similarities, but also points to specific aspects of various commercial solutions for perioperative algesimetry.

Nociception level index: do intra-operative values allow the prediction of acute postoperative pain?

Nociception Level Index (NOL) guided analgesia has previously been found to correlate with noxious stimuli during surgery. It was aim of this study to investigate the relationship between intra-operative NOL and acute postoperative pain. After IRB approval, 80 patients scheduled for non-emergency surgery were enrolled. NOL data were recorded from induction of anaesthesia until the end of surgery. After admission to the postoperative acute care unit (PACU), pain scores (numeric rating scale [NRS, 0-10] were obtained 5-minutely for 15 min. NOL data of 74 patients were analyzed. Receiver-operating curve (ROC) analysis identified the NOL reaction to the knife to skin incision (median NOL within 60 s post knife to skin) vs. the median NOL during surgery vs. NOL at the end of surgery to have the highest correlation coefficient (ρ = 0.3; P = 0.01) as well as the highest area under the ROC curve (AUC 0.68; P = 0.01) for the prediction of moderate-severe pain in PACU. A NOL > 20 after skin incision predicted moderate-severe postoperative pain with the highest combined sensitivity (73%) and specificity (58%). A NOL < 10 after skin incision excluded moderate-severe pain in PACU with a negative predictive value of 83%. The NOL reaction to skin incision, but not NOL during surgery appears to allow the exclusion and, to a lesser degree the prediction of moderate-severe pain in PACU. The results may also strengthen the manufacturers recommendation of an intraoperative NOL range of 10-25.Australian New Zealand Clinical Trials Registry: ACTRN12619001596190.

Reversal of residual neuromuscular block with neostigmine or sugammadex and postoperative pulmonary complications: a prospective, randomised, double-blind trial in high-risk older patients.

BACKGROUND: Residual neuromuscular block is associated with an increased risk of postoperative pulmonary complications in retrospective studies. The aim of our study was to investigate prospectively the incidence of postoperative pulmonary complications after reversal with either sugammadex (SUG) or neostigmine (NEO) in high-risk older patients. METHODS: We randomly allocated 180 older patients with significant morbidity (ASA physical status 3) ≥75 yr old to reversal of rocuronium with either SUG or NEO. Adverse events in the recovery room and pulmonary complications (defined by a 5-point [0-4; 0=best to 4=worst] outcome score) on postoperative Days 1, 3, and 7 were compared between groups. RESULTS: Data from 168 patients aged 80 (4) yr were analysed; SUG vs NEO resulted in a reduced probability (0.052 vs 0.122) of increased pulmonary outcome score (impaired outcome) on postoperative Day 7, but not on Days 1 and 3. More patients in the NEO group were diagnosed with radiographically confirmed pneumonia (9.6% vs 2.4%; P=0.046). The NEO group showed a non-significant trend towards longer hospital length of stay across all individual centres (combined 9 vs 7.5 days), with a significant difference in Malaysia (6 vs 4 days; P=0.011). CONCLUSIONS: Reversal of rocuronium neuromuscular block with SUG resulted in a small, but possibly clinically relevant improvement in pulmonary outcome in a select cohort of high-risk older patients. CLINICAL TRIAL REGISTRATION: ACTRN12614000108617.

Deep neuromuscular paralysis during hip arthroscopic surgery: influence on perineal tissue pressures and hip joint width.

Pudendal nerve injuries are not an uncommon side effect of patient positioning on a traction table, and muscle relaxation has been suggested to mitigate this risk by reducing pressure on the perineum. A total of 40 patients scheduled for hip arthroscopic surgery under general anaesthesia were recruited. After induction of anaesthesia, pressures on the perineum were measured in 20 subjects by means of an ultra-thin pressure sensor mat wrapped around the perineal post. Perineal pressures were assessed after the induction of anaesthesia, after leg traction and after deep muscle relaxation. In 22 subjects, the hip joint width was measured radiographically at the same time points. Pressures on the perineum were high after traction (median maximum pressure 2540 g cm-2). Neuromuscular paralysis reduced perineal pressures only minimally, but significantly (-5 g cm-2; P = 0.007). Traction increased hip joint width significantly [mean 66 (12)%; P = 0.001) and muscle relaxation further increased joint width by a mean of 3.2 (0-20)% (P = 0.001). Muscle relaxation was more beneficial for male patients (joint width increase 6.8% versus 2.8%; P = 0.04), as well as patients in whom traction alone did not achieve sufficient joint width. Muscle relaxation reduced the perineal pressure during hip arthroscopic surgery by only a negligible amount. With regard to joint space, relaxation may be of highest benefit in male patients and/or patients in whom traction alone produces only a relatively small increase in joint width (trial registration: ANZCTR 12617000191392).

Predicting acute postoperative pain by the Qnox score at the end of surgery: a prospective observational study.

BACKGROUND: The QNox score (Quantium Medical S.L., distributed by Fresenius Kabi) has recently been introduced as a tool to quantify intraoperative analgesia. Being based on the analysis of electroencephalographic data, QNox is distinctly different to other methods of nociception monitoring that rely almost entirely on the assessment of sympathetic activity. However, there are currently no published data to validate use of QNox in a clinical setting. We investigated the value of pre-arousal QNox data at the end of surgery for prediction of acute postoperative pain in the PACU. METHODS: A total of 150 patients scheduled for non-emergency surgery under sevoflurane-opioid general anaesthesia were included in the study. At the end of surgery but before patient arousal, QNox was measured minutely for 5 min. After admission to the recovery room, pain scores (numeric rating scale [NRS], 0-10) were obtained 5 minutely for 15 min. RESULTS: Data from 144 patients were analysed. QNox before arousal showed no correlation (ρ=0.057) with acute postoperative pain in the PACU. Furthermore, the score was found to have no value for the prediction of acute postoperative pain (area under the receiver operating curve, 0.501; 95% confidence interval, 0.406-0.597). CONCLUSION: QNox at the end of surgery before arousal showed no association with and allowed no prediction of acute pain in the PACU. CLINICAL TRIAL REGISTRATION: ACTRN12618001662257.

Objective monitoring of nociception: a review of current commercial solutions.

Nociception, in contrast to pain, is not a subjective feeling, but the physiological encoding and processing of nociceptive stimuli. However, monitoring nociception remains a challenge in attempts to lower the incidence of acute postoperative pain and the move towards a more automated approach to analgesia and anaesthesia. To date, several commercialised devices promise a more accurate reflection of nociception than the traditionally used vital signs, blood pressure and heart rate. This narrative review presents an overview of existing technologies and commercially available devices, and offers a perspective for future research. Although firm conclusions about individual methods may be premature, none currently appears to offer a sufficiently broad applicability. Furthermore, there is currently no firm evidence for any clinically relevant influence of such devices on patient outcome. However, the available monitors have significantly aided the understanding of underlying mechanisms and identification of potential pitfalls.

Cheaper drugs and techniques to fulfill chief executive officer perspectives - any choices?

PURPOSE OF REVIEW: Against the background of increasing healthcare costs and diminishing budgets, this review aims to present clinicians with ethically viable options to overcome budgetary restraints when seeking to introduce novel products. RECENT FINDINGS: Healthcare administrators and primary healthcare providers are not unlikely to have different opinions when discussing the introduction of novel products. However, rather than taking a 'no' for an answer, doctors may be able to argue for a change - even if this may seem to come at a higher cost. The recent introduction of the reversal agent sugammadex may provide a timely example for the possibility of success 'against all financial odds'. SUMMARY: Health professionals have the responsibility to deliver high-quality care while acknowledging the financial budget constraints. However, evidence (vs. perception) for outcome benefits of novel drugs or devices should stimulate a robust desire for their timely introduction. Demonstrating actual benefits understandable to administrators, seeking alliances with other medical specialties or patient groups, as well as negotiations with the healthcare industry may all represent viable options. Simply waiting for patents to expire should remain a measure of last resort.

Effects of muscle relaxants on ischaemia damage in skeletal muscle.

Muscle ischaemia is frequently induced intraoperatively by i.e. a surgical tourniquet or during the re-grafting phase of a free muscle transplant. The resulting muscle cell damage may impact on postoperative recovery. Neuromuscular paralysis may mitigate the effects of ischaemia. After ethics approval, 25 male Sprague-Dawley rats were anaesthetized and randomly assigned to 1 of 4 groups: Sham operation, treatment with normal saline, treatment with rocuronium (muscle relaxant) 0.6 or 1 mg kg-1, respectively. In the non-sham groups, ischaemia of one hind leg was achieved by ligation of the femoral vessels. Muscle biopsies were taken at 30 and 90 min, respectively. Cell damage was assessed in the biopsies via the expression of dystrophin, free calcium, as well as the assessment of cell viability. Pre-ischaemia muscle relaxation led to a reduction in ischaemia-induced muscle cell damage when measured by the expression of dystrophin, cell viability and the expression of free calcium even after 90 min of ischaemia (i.e. ratio control/ischaemic site for dystrophin expression after saline 0.58 ± 0.12 vs. after 1 mg/kg rocuronium 1.08 ± 0.29; P < 0.05). Muscle relaxation decreased the degree of ischaemia-induced muscle cell damage. The results may have significant clinical implications.

Current Trends in Neuromuscular Blockade, Management, and Monitoring amongst Singaporean Anaesthetists.

Introduction. This survey aimed to investigate the attitudes/practice pertaining the use, management, and monitoring of neuromuscular blockade amongst Singaporean anaesthetists. Methods. All specialist accredited anaesthetists registered with the Singapore Medical Council were invited to complete an anonymous online survey. Results. The response rate was 39.5%. Neuromuscular monitoring (NM) was used routinely by only 13.1% despite the widespread availability of monitors. 82% stated residual NMB (RNMB) was a significant risk factor for patient outcome, but only 24% believed NMB monitoring should be compulsory in all paralyzed patients. 63.6% of anaesthetists estimated the risk of RNMB in their own institutions to be <5%. 63.1% always gave reversal. Neostigmine was predominantly used (85.1%), with 28.2% using sugammadex at least sometimes, citing unavailability and high costs. However, 83.8% believed in sugammadex's benefits for patients' safety and >50% said such benefits may be able to offset the associated costs. Conclusions. There is a significant need for reeducation about RNMB, studies on local RNMB incidences, and strengthening of current monitoring practices and guidelines. Strategies are discussed. As NM monitors appear widely available and reversal of NMB standard practice, it is hopeful that Singaporean anaesthetists will change and strive for evidence-based best clinical practice to enhance patient safety.

Muscle Relaxation in Laparoscopic Surgery: What is the Evidence for Improved Operating Conditions and Patient Outcome? A Brief Review of the Literature.

When neuromuscular blocking agents (NMBA) were introduced into clinical practice in 1942, the event was called the "second revolution in anesthesia." Despite some significant side effects, NMBAs have remained in the anesthetists' repertoire, not at least because muscle relaxation has been claimed to allow or facilitate many surgical procedures. Aim of this literature review was to investigate the evidence for the use of NMBA as well as the optimum depth of neuromuscular blockade during laparoscopic surgery. Muscle relaxation may optimize laparoscopic operating conditions by preventing patient movement and achieving more intra-abdominal space for a given intra-abdominal insufflation pressure. In this context, deeper than normally maintained levels of neuromuscular blockade appear to be superior. However, the decision to utilize deeper than standard muscle relaxation should currently be based on a risk-benefit analysis for each individual patient. Thus good communication between surgeon and anesthetist remains crucial to achieve best outcomes.

Postoperative Residual Neuromuscular Paralysis at an Australian Tertiary Children's Hospital.

Purpose. Residual neuromuscular blockade (RNMB) is known to be a significant but frequently overlooked complication after the use of neuromuscular blocking agents (NMBA). Aim of this prospective audit was to investigate the incidence and severity of RNMB at our Australian tertiary pediatric center. Methods. All children receiving NMBA during anesthesia were included over a 5-week period at the end of 2011 (Mondays to Fridays; 8 a.m.-6 p.m.). At the end of surgery, directly prior to tracheal extubation, the train-of-four (TOF) ratio was assessed quantitatively. Data related to patient postoperative outcome was collected in the postoperative acute care unit. Results. Data of 64 patients were analyzed. Neostigmine was given in 34 cases and sugammadex in 1 patient. The incidence of RNMB was 28.1% overall (without reversal: 19.4%; after neostigmine: 37.5%; n.s.). Severe RNMB (TOF ratio < 0.7) was found in 6.5% after both no reversal and neostigmine, respectively. Complications in the postoperative acute care unit were infrequent, with no differences between reversal and no reversal groups. Conclusions. In this audit, RNMB was frequently observed, particularly in cases where patients were reversed with neostigmine. These findings underline the well-known problems associated with the use of NMBA that are not fully reversed.

Corrigendum: Effect of muscle relaxation on the oxygenation of human skeletal muscle: a prospective in-vivo experiment using an isolated forearm technique.

[This corrects the article on p. 13 in vol. 68, PMID: 25664149.].

Effect of muscle relaxation on the oxygenation of human skeletal muscle: a prospective in-vivo experiment using an isolated forearm technique.

BACKGROUND: Total oxygen consumption has been found to be reduced under deep neuromuscular blockade due to a lower rate of metabolism of skeletal muscles. However, the magnitude of this effect in individual muscles has not been investigated. Thus the aim of this study was to compare the oxygenation of paralyzed versus non-paralyzed forearm muscle under tourniquet-provoked ischemia. METHODS: After ethics approval and written informed consent, 30 patients scheduled for elective hand and wrist surgery were included. Ischemia was provoked by inflation of bilateral upper arm tourniquets and muscle relaxation was achieved via intravenous administration of rocuronium 0.9 mg/kg. Bilateral tourniquets were applied to both upper arms before induction of anesthesia and near infrared spectrometry (NIRS) electrodes applied on both forearms. Muscular ischemia in an isolated (= non-paralyzed, NP) as well as a paralyzed forearm (P) was created by sequential inflation of both tourniquets before and after intravenous administration of rocuronium. Muscle oxygen saturations (SmO2) of NIRS in both forearms and their changes were determined and compared. RESULTS: Data of 30 patients (15 male, 15 female; 41.8 ± 14.7 years) were analyzed. The speed of SmO2 decrease (50% decrease of SmO2 from baseline (median [percentiles]: NP 210 s [180/480s] vs. P 180 [180/300]) as well as the maximum decrease in SmO2 (minimum SmO2 in % (median [percentiles]: NP 20 [19/24] vs. P 21 [19/28]) were not significantly affected by neuromuscular paralysis. CONCLUSIONS: No significant effect of muscle relaxation on NIRS-assessed muscle oxygenation under tourniquet-induced ischemia was found in human forearm muscles.

Neuromuscular monitoring, muscle relaxant use, and reversal at a tertiary teaching hospital 2.5 years after introduction of sugammadex: changes in opinions and clinical practice.

Sugammadex was introduced to Royal Perth Hospital in early 2011 without access restriction. Two departmental audits (26-page online survey and 1-week in-theatre snapshot audit) were undertaken to investigate the change of beliefs and clinical practice related to the use of neuromuscular blocking agents at the Royal Perth Hospital since this introduction. Results were compared with data from 2011. We found that, in the 2.5 years since introduction of Sugammadex, more anesthetists (69.5 versus 38%) utilized neuromuscular monitoring, and aminosteroidal neuromuscular blocking agents were used in 94.3% of cases (versus 77% in 2011). Furthermore, 53% of anesthetists identified with a practice of "deeper and longer" intraoperative paralysis of patients. All 71 patients observed during the 5-day in-theatre audit were reversed with Sugammadex. Since the introduction of Sugammadex, 69% (n = 20) of respondents felt it provided "faster turnover," less postoperative residual neuromuscular blockade (n = 23; 79%), and higher anesthetist satisfaction (n = 17; 59%). 45% (n = 13) of colleagues reported that they would feel professionally impaired without the unrestricted availability of Sugammadex, and 1 colleague would refuse to work in a hospital without this drug being freely available. In clinical practice Sugammadex was frequently (57%) mildly overdosed, with 200 mg being the most commonly administered dose.

Retrospective investigation of postoperative outcome after reversal of residual neuromuscular blockade: sugammadex, neostigmine or no reversal.

BACKGROUND: Postoperative residual neuromuscular blockade (RNMB) is associated with significant morbidity. OBJECTIVE: The aim of this retrospective data analysis was to investigate the influence of the method of RNMB reversal on postoperative outcome. SETTING: Tertiary teaching hospital in Western Australia. PATIENTS: With Ethics Committee approval, data from 1444 patients who received at least one dose of a non-depolarising muscle relaxant intraoperatively during 2011 were analysed. MAIN OUTCOME MEASURES: Endpoints included unwanted events in the postanaesthesia care unit (PACU); symptoms of pulmonary complications within 7 postoperative days (0 to 100 outcome score based on 'temperature >38°C', 'leucocyte count >11 × 10 l', 'physical examination consistent with pneumonia' and 'shortness of breath'); PACU turnover time; and length of hospital stay. RESULTS: Data from 1444 patients (722 sugammadex, 212 neostigmine and 510 no-reversal) were analysed. The incidence of postoperative nausea and vomiting (PONV) in PACU was higher in neostigmine-reversed than sugammadex-reversed patients (21.5 vs. 13.6%; P <0.05). No differences were found regarding other PACU incidents, length of PACU stay or hospital stay. Pulmonary outcome deteriorated significantly (outcome score increased) with age and American Society of Anesthesiologists (ASA) physical status. This was observed particularly in ASA 3/4 patients more than 60 years of age in neostigmine-reversed or non-reversed patients, but almost no detrimental effect of age on pulmonary outcome was found in the sugammadex group (P <0.05). CONCLUSION: RNMB reversal with sugammadex was associated with the lowest rate of PONV and may reduce the risk of pulmonary complications in elderly ASA 3/4 patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000087853.

Acute effects of red wine on cytochrome P450 eicosanoids and blood pressure in men.

OBJECTIVE: The vasodilation accompanying acute alcohol ingestion is hard to reconcile with the strong evidence linking chronic alcohol consumption with hypertension. Cytochrome P450 (CYP450) eicosanoids derived from arachidonic acid include vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20-hydroxyeicosatrienoic acid (20-HETE). This study aimed to examine the relationship between CYP450 eicosanoids and blood pressure (BP), and compared the effect of single session of drinking red wine with de-alcoholized red wine (DRW) or water over 24 h. METHODS: Twenty-five normotensive men were randomly assigned to drink either 375 ml of red wine (41 g of alcohol) or the equivalent volume of DRW or water, with a light meal on 3 separate days. Ambulatory BP and heart rate were measured over 24 h. Blood samples were obtained before and 2, 4 and 24 h after beverage consumption. RESULTS: Blood pressure fell in the first 4 h after red wine consumption (P = 0.001), but was significantly higher after 20 h (P = 0.037). Plasma 20-HETE fell in the 2 h after consumption of all beverages, but over the 24-h period was relatively higher after red wine consumption (P = 0.025). The largest difference in 20-HETE was 2 h after consuming red wine and coincided with the highest blood alcohol level. There were no significant effects of red wine on plasma EETs. CONCLUSION: Acute consumption of alcohol as red wine results in a relative increase in plasma levels of the vasoconstrictor 20-HETE over 24 h without affecting EETs, and may contribute to the BP elevation that associates with a binge drinking pattern or be a homeostatic response to the acute fall in BP induced by alcohol.

Introduction of sugammadex as standard reversal agent: Impact on the incidence of residual neuromuscular blockade and postoperative patient outcome.

BACKGROUND: The aim of this prospective audit was to investigate clinical practice related to muscle relaxant reversal and the impact made by the recent introduction of sugammadex on patient outcome at a tertiary teaching hospital. METHODS: Data from all patients intubated at our institution during two epochs of seven consecutive days each was collected prospectively. Directly prior to extubation, the train-of-four (TOF) ratio was assessed quantitatively by an independent observer. Postoperative outcome parameters were complications in the recovery room and radiological diagnosed atelectasis or pneumonia within 30 days. RESULTS: Data from 146 patients were analysed. Three reversal strategies were used: no reversal, neostigmine or sugammadex. The TOF ratio was less than 0.7 in 17 patients (nine no reversal, eight neostigmine) and less than 0.9 in 47 patients (24 no reversal, 19 neostigmine, four sugammadex). Those reversed with sugammadex showed fewer episodes of postoperative oxygen desaturation (15% vs. 33%; P<0.05). TOF ratios of less than 0.7 (P<0.05) and also <0.9 (P<0.01) were more likely associated with X-ray results consistent with postoperative atelectasis or pneumonia. CONCLUSIONS: Our results suggest a significant impact of residual paralysis on patient outcome. The use of sugammadex resulted in the lowest incidence of residual paralysis.