Generalizability of nociception level as a measure of intraoperative nociceptive stimulation: A retrospective analysis.

BACKGROUND: Nociception-guided intraoperative opioid administration might help reduce postoperative pain. A commonly used and validated nociception monitor system is nociception level (NOL), which provides the nociception index, ranging from 0 to 100, with 0 representing no nociception and 100 representing extreme nociception. We tested the hypothesis that NOL responses are similar in men and women given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies. METHODS: We conducted a retrospective cohort analysis of trial data from eight prospective NOL validation studies. Among 522 noncardiac surgical patients enrolled in these studies, 447 were included in our analysis. We assessed NOL responses to various noxious and non-noxious stimuli. RESULTS: The average NOL in response to 315 noxious stimuli was 47 ± 15 (95% CI = 45-49). The average NOL in response to 361 non-noxious stimuli was 10 ± 12 (95% CI = 9-11). NOL responses were similar in men and women, in patients given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies. CONCLUSION: Nociception level appears to provide accurate estimates of intraoperative nociception over a broad range of patients and anesthetic conditions.

Effects of obesity, pneumoperitoneum, and body position on mechanical power of intraoperative ventilation: an observational study.

Mechanical power can describe the complex interaction between the respiratory system and the ventilator and may predict lung injury or pulmonary complications, but the power associated with injury of healthy human lungs is unknown. Body habitus and surgical conditions may alter mechanical power but the effects have not been measured. In a secondary analysis of an observational study of obesity and lung mechanics during robotic laparoscopic surgery, we comprehensively quantified the static elastic, dynamic elastic, and resistive energies comprising mechanical power of ventilation. We stratified by body mass index (BMI) and examined power at four surgical stages: level after intubation, with pneumoperitoneum, in Trendelenburg, and level after releasing the pneumoperitoneum. Esophageal manometry was used to estimate transpulmonary pressures. Mechanical power of ventilation and its bioenergetic components increased over BMI categories. Respiratory system and lung power were nearly doubled in subjects with class 3 obesity compared with lean at all stages. Power dissipated into the respiratory system was increased with class 2 or 3 obesity compared with lean. Increased power of ventilation was associated with decreasing transpulmonary pressures. Body habitus is a prime determinant of increased intraoperative mechanical power. Obesity and surgical conditions increase the energies dissipated into the respiratory system during ventilation. The observed elevations in power may be related to tidal recruitment or atelectasis, and point to specific energetic features of mechanical ventilation of patients with obesity that may be controlled with individualized ventilator settings.NEW & NOTEWORTHY Mechanical power describes the complex interaction between a patient's lungs and the ventilator and may be useful in predicting lung injury. However, its behavior in obesity and during dynamic surgical conditions is not understood. We comprehensively quantified ventilation bioenergetics and effects of body habitus and common surgical conditions. These data show body habitus is a prime determinant of intraoperative mechanical power and provide quantitative context for future translation toward a useful perioperative prognostic measurement.

Comparison of the Conox (qCON) and Sedline (PSI) depth of anaesthesia indices to predict the hypnotic effect during desflurane general anaesthesia with ketamine.

Comparison of two depth of anesthesia indices, qCON (Conox) and PSI (Sedline), during desflurane sedation and their sensitivity to random ketamine boluses in patients undergoing routine surgery. The performance of desflurane and ketamine on both indices was analyzed for 11 patients, and the ketamine sensitivity was compared with another group of 11 patients under sevoflurane and propofol.The MOAA/S was used to determine sedation level and pain. Different boluses of ketamine ranging from 10 to 30 mg where randomly administered in both groups and the effect on the indexes were measured after 4 min.The indices were recorded during the whole surgery, and their correlations with the desflurane concentration and the discrimination between awake and anesthetized states were evaluated with the prediction probability statistic (Pk). The Pk values, mean (se), discriminating between awake and anesthetized states were 0.974(0.016) for the qCON and 0.962(0.0123) for the PSI, while the 1-Pk statistic for the qCON and the PSI with respect to the desflurane concentration were 0.927(0.016) and 0.918(0.018), respectively, with no statistically significant differences.The agreement between both depth of hypnosis parameters was assessed under the Bland-Altman plot and the Spearman correlation, rs = 0.57(p < 0.001).During the sevoflurane-propofol anesthesia, which served as a control group, both indices experienced a similar behavior with a no significant change of their median values after ketamine. However, during desflurane anesthesia the qCON index did not change significantly after ketamine administration, qCON (before = 33 (4), after = 30 (17); Wilcoxon, p = 0.89), while the PSI experienced a significant increase, PSI (before = 31(6), after = 39(16) Wilcoxon, p = 0.013).This study shows that qCON and PSI have similar performance under desflurane with good discrimination between the awake and anesthetized states. While both indices exhibited similar behavior under ketamine boluses under a sevoflurane-propofol anesthesia, the qCON index had a better performance under ketamine during desflurane anesthesia.

Pain monitor: reality or fantasy in ambulatory patients.

PURPOSE OF REVIEW: In an unconscious patient, there can be significant challenges to monitoring nociception and proper dosing of analgesic medications. The traditional measures of intraoperative nociception have poor sensitivity and specificity with little predictive value in postoperative outcomes such as postoperative pain, opioid-induced side effects, length of stay or incidence of opioid use disorder. To date, several monitoring modalities are in development to establish objective measures of the balance between nociception and analgesia with the goal of guiding anesthesiologists and improve patient outcomes. In this review, some of the most promising monitoring modalities are discussed with the most recent findings. RECENT FINDINGS: Multiple modalities are beginning to demonstrate utility compared with traditional care. Most, but not all, of these studies show decreased intraoperative opioid use and some show lower pain scores and opioid requirements in the postanesthesia care unit. SUMMARY: Recent evidence points to promising efficacy for these monitoring modalities; however, this field is in its infancy. More investigation is required to demonstrate differences in outcome compared with traditional care, and these differences need to be of sufficient import to achieve widespread adoption.

Thromboelastography Before Epidural Placement in a Thrombocytopenic Parturient With Gaucher Disease Treated With Imiglucerase: A Case Report.

Gaucher disease is a common inborn error of metabolism leading to widespread chronic inflammation and often thrombocytopenia. Here we discuss assessment of coagulation in a parturient with Gaucher disease treated with imiglucerase, who presented with thrombocytopenia and requested epidural analgesia for planned vaginal delivery. We used thromboelastography to determine the safety of placing an epidural catheter and to plan for potential peripartum bleeding. The patient had a normal coagulation profile by thromboelastography and had uncomplicated epidural analgesia for a successful spontaneous vaginal delivery.

Venous pressure during intravenous regional anesthesia: Implications for setting tourniquet pressure.

BACKGROUND AND AIMS: Intravenous regional anesthesia (IVRA) is utilized for upper extremity surgery, but higher tourniquet pressure and longer inflation time increase the risk of soft tissue and nerve injury. We investigated the duration and magnitude of elevated venous pressure during IVRA to assess the possibility of safely lowering the tourniquet pressure during surgery. MATERIAL AND METHODS: Twenty adult patients scheduled for distal upper extremity surgery were enrolled. An additional intravenous catheter was placed in the surgical arm connected to a digital pressure transducer for monitoring venous pressure. Venous pressure was recorded prior to IVRA and every 30 s after injection of local anesthetic (LA) until the completion of surgery. RESULTS: All 20 subjects completed the study without complication. Peak venous pressure was 340 mmHg in one patient which lasted for less than 30 s. Mean venous pressures fell below systolic blood pressure after 4.5 min in all cases except one. This patient had elevated venous pressures for 24 of 25 min of tourniquet time exceeding systolic blood pressure. The only statistically significant intraoperative factor associated with elevated venous pressure was elevated peak systolic pressure (P = 0.001). CONCLUSIONS: We found that the mean peak venous pressure was below systolic blood pressure in only 14 of the 20 subjects, and the peak injection pressure exceeded 300 mmHg in one patient. Another patient's venous pressure remained above systolic blood pressure for 24 of 25 min of tourniquet time. Current precautions to prevent LA toxicity may be insufficient in some patients and attempts to lower tourniquet pressures to just above systolic blood pressures soon after IVRA injection may result in toxicity, specifically if systolic pressure is elevated.

The Effect of Zinc Lozenge on Postoperative Sore Throat: A Prospective Randomized, Double-Blinded, Placebo-Controlled Study.

BACKGROUND: Postoperative sore throat (POST) is commonly seen after endotracheal intubation, and oral zinc prevents oral mucositis associated with chemotherapy. This study is designed to evaluate the effects of administration of zinc lozenges on POST. METHODS: Seventy-nine patients undergoing low- or moderate-risk surgery with endotracheal intubation were randomly assigned into 2 groups: Control group received placebo and zinc group received 40-mg zinc lozenges 30 minutes preoperatively. Patients were assessed for incidence and severity (4-point scale, 0-3) of POST at 0, 2, 4, and 24 hours postoperatively. The primary outcome was incidence of POST at 4 hours after surgery. The secondary outcomes were the incidence of POST at 0, 2, and 24 hours and the severity of POST. RESULTS: At 4 hours, there was a significantly lower incidence of POST in the zinc group, 7%, than the control group, 29% (P = .046). The incidence of POST at 0 hour was 0% in zinc group and 24% in control group (P = .004). The highest incidence of POST occurred at the second hour after surgery, with the rate of 10% in the zinc group and 34% in the control group (P = .0495). The incidence of POST at 24 hours was 13% in zinc group and 24% in control group (not significant). The severity of POST was significantly lower in the zinc group for mild (P = .003) and moderate (P = .004) POST. CONCLUSIONS: The administration of a single dose of 40-mg zinc lozenge 30 minutes preoperatively is effective to reduce both incidence of POST in the first 4 hours and severity of mild and moderate POST in the immediate postoperative period.

The role of the NOP receptor in regulating food intake, meal pattern, and the excitability of proopiomelanocortin neurons.

We evaluated the role of the nociceptin/orphanin FQ (NOP) receptor in regulating food intake, meal pattern and the activity of hypothalamic arcuate (ARC) neurons. The microstructural analysis of food intake and meal pattern was performed under both food-deprived and ad libitum conditions. Whole-cell patch clamp recordings were obtained using the in vitro hypothalamic slice preparation and biocytin-filled electrodes. NOP receptor knockout mice exhibited significantly reduced body weight. Fasting-induced hyperphagia was diminished for the first 2h of a 6-h re-feeding period, and was associated with decreased meal duration and size, as well as a biphasic effect on meal frequency. The genotype effect observed under ad libitum conditions was comparatively unremarkable. Orphanin FQ/nociceptin (OFQ/N) was able to decrease evoked excitatory postsynaptic current amplitude, increase the S(2):S(1) ratio via the paired-pulse paradigm, and decrease miniature excitatory postsynaptic current frequency in ARC neurons from wild type animals but not NOP receptor knockouts. In addition OFQ/N activated a reversible outward current that was antagonized by the G-protein activated, inwardly-rectifying K(+) (GIRK) channel blocker tertiapin in wild type but not NOP knockout animals. Both the presynaptic and postsynaptic actions of OFQ/N were observed in ARC neurons subsequently determined to be immunopositive for characteristic phenotypic markers of anorexigenic proopiomelanocortin (POMC) neurons. Taken together, these results demonstrate the contribution of the NOP receptor in controlling food intake and meal pattern, as well as glutamate release and GIRK1 channel activity at POMC synapses.

Sex differences in the cannabinoid regulation of energy homeostasis.

This review highlights the progress made thus far in characterizing the behavioral and cellular mechanisms through which cannabinoids regulate energy homeostasis. We performed microstructural analysis of feeding behavior in gonadectomized guinea pigs and gonadally intact, transgenic CB1 receptor knockout mice to determine how cannabinoids affect circadian rhythms in food intake and meal pattern. We also implanted data loggers into the abdominal cavity to correlate the appetite-modulating properties of cannabinoids with changes in core body temperature. We then coupled the effects on feeding behavior and temperature regulation with synaptic changes in the hypothalamic feeding circuitry via whole-cell patch clamp electrophysiological recording from neurons in the arcuate nucleus (ARC), in order to gain a more global perspective on the cannabinoid modulation of energy homeostasis. We observed marked sex differences in cannabinoid effects on food intake and core body temperature--with male guinea pigs exhibiting a comparatively greater sensitivity to the hyperphagia and hypophagia, as well as the hypothermia and hyperthermia, produced by CB1 receptor agonists and antagonists, respectively. In addition, male but not female CB1 receptor knockout mice show a diminished nocturnal food intake and average daily body weight relative to their wildtype littermate controls. The disparity in the CB1 receptor-mediated hyperphagia is paralleled by sex differences in the cellular effects of cannabinoids at anorexigenic, guinea pig proopiomelanocortin (POMC) synapses. Postsynaptically, cannabinoids potentiate an A-type K+ current (I(A)) in POMC neurons from female guinea pigs, whereas in males the activation of an inwardly rectifying K+ current is observed. Presynaptically, while cannabinoids inhibit glutamatergic input onto POMC neurons in males and females to similar degrees, males are more refractory to the cannabinoid-induced inhibition of convergent GABAergic input than females. These data reveal pervasive sex differences in the cannabinoid regulation of energy homeostasis that are consistent with changes in the excitability of POMC neurons.

Sex differences in the cannabinoid modulation of appetite, body temperature and neurotransmission at POMC synapses.

We sought to determine whether sex differences exist for the cannabinoid modulation of appetite, body temperature and neurotransmission at pro-opiomelanocortin (POMC) synapses. Gonadectomized male and female guinea pigs were outfitted to monitor core body temperature and injected with either the CB1 receptor agonist WIN 55,212-2 (1 mg/kg s.c.), antagonist AM251 (3 mg/kg s.c.) or vehicle (1 ml/kg s.c.) and evaluated for changes in six indices of feeding behavior under ad libitum conditions for 7 days. WIN 55,212-2 elicited an overt, sexually differentiated hyperphagia in which males displayed larger increases in hourly and daily intake, consumption/gram body weight, meal size and meal duration. The agonist also produced a more robust acute hypothermia in males than in females. In addition, males were more sensitive to the hypophagic effect of AM251, manifested by comparatively sizeable decreases in hourly intake, consumption/gram body weight, meal frequency and hyperthermia. To gain additional insight into the cellular mechanism underlying cannabinoid regulation of energy homeostasis, we performed whole-cell patch clamp recordings in hypothalamic slices prepared from gonadectomized male and female guinea pigs, and monitored miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) in arcuate (ARC) neurons. ARC neurons from females exhibited a higher basal mEPSC frequency. WIN 55,212-2 dose-dependently reduced mEPSC and mIPSC frequency; however, cells from males were far less sensitive to the CB1 receptor-mediated decrease in mIPSC frequency. These effects were observed in neurons subsequently identified as POMC neurons. These data reveal pronounced sex differences in how cannabinoids influence the hypothalamic control of homeostasis.