Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

A randomised crossover trial comparing the Airtraq ® NT, McGrath ® MAC and Macintosh laryngoscopes for nasotracheal intubation of simulated easy and difficult airways in a manikin / Estudo cruzado e randômico comparando os laringoscópios Airtraq ® NT, McGrath ® MAC e Macintosh para intubação nasotraqueal em simulação de via aérea fácil e difícil em manequim

ABSTRACT OBJECTIVE: Several devices can aid nasotracheal intubation when managing difficult airways. The McGrath MAC and Airtraq NT were compared with a Macintosh laryngoscope when studying the performance of anaesthetists with different levels of experience, in a manikin model of easy or difficult airway scenarios. METHODS: Sixty-three anaesthetists were recruited into a randomised trial in which each performed nasotracheal intubation with all laryngoscopes, in both scenarios. The main endpoint was intubation time. Additional endpoints included laryngoscopic view, intubation success, number of optimisation manoeuvres, audible dental clicks and the force applied to the upper airway. RESULTS: Intubation time was significantly shorter using the McGrath MAC in both scenarios and using the Airtraq in the difficult scenario, when compared with the Macintosh laryngoscope. Both devices gave more Cormack and Lehane grade 1 or 2 views than the Macintosh in the difficult scenario (p < 0.001). The McGrath MAC had the best first-attempt success rate (98.4% vs. 96.8% and 95.8%, p < 0.001 for the Airtraq NT and Macintosh laryngoscopes respectively). The number of optimisation manoeuvres, audible dental clicks and subjective assessment of the degree of force applied were significantly lower for indirect laryngoscopes versus the Macintosh laryngoscope (p < 0.001). CONCLUSION: In a manikin, the Airtraq and the McGrath laryngoscopes appeared superior to the Macintosh laryngoscope when dealing with simulated airway scenarios. Both devices were associated with better views, intubation times and rates of success, especially in a simulated "difficult airway". Overall satisfaction was highest with the McGrath laryngoscope. Similar clinical studies are needed.

RESUMO OBJETIVO: Vários dispositivos podem ajudar a intubação nasotraqueal no manejo de via aérea difícil. Os laringoscópios McGrath MAC e Airtraq NT foram comparados com um laringoscópio Macintosh em estudo do desempenho de anestesistas com diferentes níveis de experiência, em manequim com cenário de via aérea fácil ou difícil. MÉTODOS: Foram recrutados 63 anestesistas para um estudo randômico, no qual cada um fez intubação nasotraqueal com todos os laringoscópios, em ambos os cenários. O desfecho primário foi o tempo de intubação. Desfechos adicionais incluíram vista laringoscópica, sucesso na intubação, número de manobras de aprimoramento, cliques dentais audíveis e força aplicada nas vias aéreas superiores. RESULTADOS: O tempo de intubação foi significativamente menor com o uso do laringoscópio McGrath MAC em ambos os cenários e com o uso do Airtraq no cenário difícil, em comparação com o laringoscópio Macintosh. Ambos os dispositivos obtiveram mais grau 1 ou 2 de Cormack e Lehane para visualização do que o Macintosh em cenário difícil (p < 0,001). O McGrath MAC teve a melhor taxa de sucesso na primeira tentativa (98,4% vs. 96,8% e 95,8%, p < 0,001, para os laringoscópios Airtraq NT e Macintosh, respectivamente). O número de manobras de aprimoramento, os cliques dentais audíveis e a avaliação subjetiva do grau de força aplicada foram significativamente menores para os laringoscópios indiretos versus o laringoscópio Macintosh (p < 0,001). CONCLUSÃO: Em um manequim, os laringoscópios Airtraq e McGrath pareceram superiores ao laringoscópio Macintosh para lidar com cenários das vias aéreas simuladas. Ambos os dispositivos foram associados a melhores visibilidades, tempos de intubação e taxas de sucesso, especialmente em simulação de "via aérea difícil". A satisfação geral foi maior com o laringoscópio McGrath. Estudos clínicos similares são necessários.

A randomised crossover trial comparing the Airtraq(®) NT, McGrath(®) MAC and Macintosh laryngoscopes for nasotracheal intubation of simulated easy and difficult airways in a manikin.

OBJECTIVE: Several devices can aid nasotracheal intubation when managing difficult airways. The McGrath MAC and Airtraq NT were compared with a Macintosh laryngoscope when studying the performance of anaesthetists with different levels of experience, in a manikin model of easy or difficult airway scenarios. METHODS: Sixty-three anaesthetists were recruited into a randomised trial in which each performed nasotracheal intubation with all laryngoscopes, in both scenarios. The main endpoint was intubation time. Additional endpoints included laryngoscopic view, intubation success, number of optimisation manoeuvres, audible dental clicks and the force applied to the upper airway. RESULTS: Intubation time was significantly shorter using the McGrath MAC in both scenarios and using the Airtraq in the difficult scenario, when compared with the Macintosh laryngoscope. Both devices gave more Cormack and Lehane grade 1 or 2 views than the Macintosh in the difficult scenario (p<0.001). The McGrath MAC had the best first-attempt success rate (98.4% vs. 96.8% and 95.8%, p<0.001 for the Airtraq NT and Macintosh laryngoscopes respectively). The number of optimisation manoeuvres, audible dental clicks and subjective assessment of the degree of force applied were significantly lower for indirect laryngoscopes versus the Macintosh laryngoscope (p<0.001). CONCLUSION: In a manikin, the Airtraq and the McGrath laryngoscopes appeared superior to the Macintosh laryngoscope when dealing with simulated airway scenarios. Both devices were associated with better views, intubation times and rates of success, especially in a simulated "difficult airway". Overall satisfaction was highest with the McGrath laryngoscope. Similar clinical studies are needed.

Severe Nausea and Vomiting in the Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia II Trial.

BACKGROUND: The Evaluation of Nitrous oxide in the Gas Mixture for Anesthesia II trial randomly assigned 7,112 noncardiac surgery patients to a nitrous oxide or nitrous oxide-free anesthetic; severe postoperative nausea and vomiting (PONV) was a prespecified secondary end point. Thus, the authors evaluated the association between nitrous oxide, severe PONV, and effectiveness of PONV prophylaxis in this setting. METHODS: Univariate and multivariate analyses of patient, surgical, and other perioperative characteristics were used to identify the risk factors for severe PONV and to measure the impact of severe PONV on patient outcomes. RESULTS: Avoiding nitrous oxide reduced the risk of severe PONV (11 vs. 15%; risk ratio [RR], 0.74 [95% CI, 0.63 to 0.84]; P < 0.001), with a stronger effect in Asian patients (RR, 0.55 [95% CI, 0.43 to 0.69]; interaction P = 0.004) but lower effect in those who received PONV prophylaxis (RR, 0.89 [95% CI, 0.76 to 1.05]; P = 0.18). Gastrointestinal surgery was associated with an increased risk of severe PONV when compared with most other types of surgery (P < 0.001). Patients with severe PONV had lower quality of recovery scores (10.4 [95% CI, 10.2 to 10.7] vs. 13.1 [95% CI, 13.0 to 13.2], P < 0.0005); severe PONV was associated with postoperative fever (15 vs. 20%, P = 0.001). Patients with severe PONV had a longer hospital stay (adjusted hazard ratio, 1.14 [95% CI, 1.05 to 1.23], P = 0.002). CONCLUSIONS: The increased risk of PONV with nitrous oxide is near eliminated by antiemetic prophylaxis. Severe PONV, which is seen in more than 10% of patients, is associated with postoperative fever, poor quality of recovery, and prolonged hospitalization.

Nitrous Oxide and Serious Long-term Morbidity and Mortality in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II Trial.

BACKGROUND: The Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II trial randomly assigned 7,112 noncardiac surgery patients at risk of perioperative cardiovascular events to 70% N2O or 70% N2 groups. The aim of this follow-up study was to determine the effect of nitrous oxide on a composite primary outcome of death and major cardiovascular events at 1 yr after surgery. METHODS: One-year follow-up was conducted via a medical record review and telephone interview. Disability was defined as a Katz index of independence in activities of daily living score less than 8. Adjusted odds ratios and hazard ratios were calculated as appropriate for primary and secondary outcomes. RESULTS: Among 5,844 patients evaluated at 1 yr, 435 (7.4%) had died, 206 (3.5%) had disability, 514 (8.8%) had a fatal or nonfatal myocardial infarction, and 111 (1.9%) had a fatal or nonfatal stroke during the 1-yr follow-up period. Exposure to nitrous oxide did not increase the risk of the primary outcome (odds ratio, 1.08; 95% CI, 0.94 to 1.25; P = 0.27), disability or death (odds ratio, 1.07; 95% CI, 0.90 to 1.27; P = 0.44), death (hazard ratio, 1.17; 95% CI, 0.97 to 1.43; P = 0.10), myocardial infarction (odds ratio, 0.97; 95% CI, 0.81 to 1.17; P = 0.78), or stroke (odds ratio, 1.08; 95% CI, 0.74 to 1.58; P = 0.70). CONCLUSION: These results support the long-term safety of nitrous oxide administration in noncardiac surgical patients with known or suspected cardiovascular disease.

The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial.

BACKGROUND: Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk. METHODS: We did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients' group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at ClinicalTrials.gov, number NCT00430989. FINDINGS: Of 10,102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83­1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001). INTERPRETATION: Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection, the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis, and a desired effect of reduced volatile agent use was shown. FUNDING: Australian National Health and Medical Research Council; Australian and New Zealand College of Anaesthetists; Heart and Stroke Foundation of Quebec, Heart and Stroke Foundation of Ontario, Canada; General Research Fund of the Research Grant Council, Hong Kong Special Administrative Region, China.

Prophylactic ondansetron does not prevent shivering or decrease shivering severity during cesarean delivery under combined spinal epidural anesthesia: a randomized trial.

OBJECTIVES: Cesarean delivery is commonly performed under regional anesthesia, which is often associated with maternal shivering. This can cause distress and interfere with monitoring. The study objective was to evaluate the antishivering efficacy of ondansetron, which reduces the incidence and severity of shivering in nonobstetric patients. We hypothesized that there would be a significant decrease in the incidence and/or severity of shivering in women who are given intravenous ondansetron 8 mg before combined spinal epidural (CSE) anesthesia, when compared with placebo. METHODS: This was a randomized, double-blinded, parallel-group, placebo-controlled trial of 118 women scheduled for elective cesarean surgery. Women received either intravenous ondansetron 8 mg (n = 58) or saline (n = 60) before CSE anesthesia (intrathecal hyperbaric bupivacaine 0.5% 2.2-2.5 mL plus fentanyl 15 µg). The incidence and severity of shivering, measured on a validated 5-point scale, and other outcomes, such as nausea, pruritus, headache, or satisfaction, were assessed at 3 time points during the surgery and postoperative period. RESULTS: The incidence of shivering at any time point did not differ significantly between groups: ondansetron 41% versus placebo 47% (P = 0.54). The incidence of severe shivering at any time was not significantly different: ondansetron 32% versus placebo 33% (P = 0.79). There were no significant differences between the groups for any secondary outcomes. CONCLUSIONS: Intravenous ondansetron 8 mg before performing CSE anesthesia in women undergoing elective cesarean delivery does not decrease the incidence or severity of shivering.

A phase I pharmacokinetic and bioavailability study of a sublingual fentanyl wafer in healthy volunteers.

BACKGROUND: The sublingual administration of opioids is a simple and noninvasive method that provides rapid analgesia. In this phase I study we investigated the pharmacokinetics and bioavailability of a fentanyl wafer in healthy volunteers. The principal study objective was to investigate the pharmacokinetic profile of a new sublingual fentanyl wafer and to establish its absolute bioavailability. METHODS: Twenty-four healthy volunteers, mean age 23 years, were randomly assigned to receive the equivalent of fentanyl 100 µg by both the sublingual and IV routes. Blood samples were collected in sterile polypropylene tubes for 24 hours after each fentanyl administration. The pharmacokinetic parameters were determined by model-independent pharmacokinetic analyses of the plasma fentanyl concentration-time profiles. RESULTS: The mean absolute bioavailability of the sublingual fentanyl wafer was 78.9% (90% confidence interval [CI] 51.1% to 121.7%). The first detectable plasma fentanyl concentration time ranged from 2 to 10 minutes in all volunteers, and the mean (±SD) time to peak plasma concentration at 0.91 (±0.73) hours after administration. CONCLUSION: Sublingual administration of fentanyl as a wafer product resulted in rapidly detectable plasma fentanyl concentrations. The absolute bioavailability of 78.9% indicated a high systemic availability of fentanyl and suggests that further development of this wafer is justified.

A cost-benefit analysis of the ENIGMA trial.

BACKGROUND: The ENIGMA trial was a prospective, randomized, multicenter study that evaluated the clinical consequences of including N2O in general anesthesia. Patients who were given a N2O-free anesthetic when undergoing major surgery for which the expected hospital stay was at least 3 days had lower rates of some postoperative complications. This suggests that, despite a higher consumption of potent inhalational agent, there could be a financial benefit when N2O is avoided in such settings. METHODS: A retrospective cost analysis of the 2,050 patients recruited to the ENIGMA trial was performed. We measured costs from the perspective of an implementing hospital. Direct health care costs include the costs for maintaining anesthesia, daily medications, hospitalization, and complications. The primary outcome was the net financial savings from avoiding N2O in major noncardiac surgery. Comparisons between groups were analyzed using Student t test and bootstrap methods. Sensitivity analyses were also performed. RESULTS: Rates of some serious complications were higher in the N2O group. Total costs in the N2O group were $16,203 and in the N2O-free group $13,837, mean difference of $2,366 (95% CI: 841-3,891); P = 0.002. All sensitivity analyses retained a significant difference in favor of the N2O-free group (all P ≤ 0.005). CONCLUSIONS: Despite N2O reducing the consumption of more expensive potent inhalational agent, there were marked additional costs associated with its use in adult patients undergoing major surgery because of an increased rate of complications. There is no cogent argument to continue using N2O on the basis that it is an inexpensive drug.

Nitrous oxide and long-term morbidity and mortality in the ENIGMA trial.

BACKGROUND: There is a plausible pathophysiologic rationale for increased long-term cardiovascular morbidity and mortality in patients receiving significant exposure to nitrous oxide. However, this relationship has not been established clinically. The ENIGMA trial randomized 2050 patients having noncardiac surgery lasting more than 2 hours to nitrous oxide-based or nitrous oxide-free anesthesia. We conducted a follow-up study of the ENIGMA patients to evaluate the risk of cardiovascular events in the longer term. METHODS: The trial case report forms and medical records of all study patients were reviewed. The date and cause of death and occurrence of myocardial infarction or stroke were recorded. A telephone interview was then conducted with all surviving patients. The primary endpoint of the study was survival. RESULTS: The median follow-up time was 3.5 (range: 0 to 5.7) years. Three hundred eighty patients (19%) had died since the index surgery, 91 (4.5%) were recorded as having myocardial infarction, and 44 (2.2%) had a stroke during the entire follow-up period. Nitrous oxide did not significantly increase the risk of death [hazard ratio = 0.98 (95% confidence interval, CI: 0.80 to 1.20; P = 0.82)]. The adjusted odds ratio for myocardial infarction in patients administered nitrous oxide was 1.59 (95% CI: 1.01 to 2.51; P = 0.04) and for stroke was 1.01 (95% CI: 0.55 to 1.87; P = 0.97). CONCLUSIONS: The administration of nitrous oxide was associated with increased long-term risk of myocardial infarction, but not of death or stroke in patients enrolled in the ENIGMA trial. The exact relationship between nitrous oxide administration and serious long-term adverse outcomes will require confirmation by an appropriately designed large randomized controlled trial.

Dreaming and electroencephalographic changes during anesthesia maintained with propofol or desflurane.

BACKGROUND: Dream recall is reportedly more common after propofol than after volatile anesthesia, but this may be due to delayed emergence or more amnesia after longer-acting volatiles. The electroencephalographic signs of dreaming during anesthesia and the differences between propofol and desflurane also are unknown. The authors therefore compared dream recall after propofol- or desflurane-maintained anesthesia and analyzed electroencephalographic patterns in dreamers and nondreamers and in propofol and desflurane patients for similarities to rapid eye movement and non-rapid eye movement sleep. METHODS: Three hundred patients presenting for noncardiac surgery were randomized to receive propofol- or desflurane-maintained anesthesia. The raw electroencephalogram was recorded from induction until patients were interviewed about dreaming when they became first oriented postoperatively. Using spectral and ordinal methods, the authors quantified the amount of sleep spindle-like activity and high-frequency power in the electroencephalogram. RESULTS: The incidence of dream recall was similar for propofol (27%) and desflurane (28%) patients. Times to interview were similar (median 20 [range 4-114] vs. 17 [7-86] min; P = 0.1029), but bispectral index values at interview were lower (85 [69-98] vs. 92 [40-98]; P < 0.0001) in propofol than in desflurane patients. During surgery, the raw electroencephalogram of propofol patients showed more and faster spindle activity than in desflurane patients (P < 0.001). The raw electroencephalogram of dreamers showed fewer spindles and more high-frequency power than in nondreamers in the 5 min before interview (P < 0.05). CONCLUSIONS: Anesthetic-related dreaming seems to occur just before awakening and is associated with a rapid eye movement-like electroencephalographic pattern.

Nitrous oxide and perioperative cardiac morbidity (ENIGMA-II) Trial: rationale and design.

BACKGROUND: Globally there are >200 million major surgical procedures undertaken annually, and about 20% of these involve patients who have coronary artery disease. Many receive nitrous oxide, which impairs methionine synthase, thus inhibiting folate synthesis and increasing postoperative homocysteine levels. Nitrous oxide anesthesia leads to postoperative endothelial dysfunction, and there is some evidence that it increases myocardial ischemia and, possibly, myocardial infarction. We have initiated the Nitrous oxide and perioperative cardiac morbidity (ENIGMA-II) Trial to test the hypothesis that in inpatients undergoing anesthesia for major noncardiac surgery, avoidance of nitrous oxide will reduce the incidence of death and major cardiovascular events. METHODS: ENIGMA-II is a 7,000-patient, international randomized trial involving patients at risk of coronary artery disease undergoing noncardiac surgery. The patients, health care providers (except for the anesthesiologists), data collectors, and outcome adjudicators are blinded to whether patients receive nitrous oxide-containing or nitrous oxide-free anesthetic. The primary outcome is a composite of death and major nonfatal events (ie, myocardial infarction, cardiac arrest, pulmonary embolism, and stroke) at 30 days after surgery. RESULTS: At present, ENIGMA-II has randomized >1,000 patients in 22 hospitals in 5 countries. To date, patients' mean age is 70 years, 66% are men, 38% have a history of coronary artery disease, 19% have a history of cerebrovascular disease, and 84% have a history of hypertension. Most patients have undergone intra-abdominal 28%, vascular 32%, and orthopedic 16% surgery. CONCLUSIONS: The ENIGMA-II Trial will be the largest study yet conducted to ascertain the benefits and risks of removing nitrous oxide from the gas mixture in anesthesia. The results of this large international trial will guide the clinical care of the hundreds of millions of adults undergoing noncardiac surgery annually.

Neuroanesthesia for the pregnant woman.

Neuroanesthesia for the pregnant patient is required infrequently, and evidence-based recommendations for neuroanesthetic management are sparse. We present a framework for a practical approach to anesthesia of the pregnant patient with subarachnoid or intracerebral hemorrhage, intracranial tumor, traumatic brain injury, spinal tumor, or spinal injury. The importance of a team-approach is emphasized. The anesthesiologist may have to anesthetize the pregnant patient for neurosurgery well before delivery, for cesarean delivery at the time of the neurosurgical procedure, or for delivery after neurosurgery. These scenarios are discussed along with fetal safety and anesthetic considerations for interventional neuroradiology.

The clinical applications of intranasal opioids.

Opioids are widely used in all fields of pain management and may be delivered by a number of routes of administration. The intranasal administration of opioid is a convenient route of transmucosal drug delivery that has received limited attention. Potential advantages compared with parenteral or oral administration include avoidance of painful injection, avoidance of risks associated with intravenous access, rapid onset and titration to effect, good bioavailability, and high levels of acceptability and familiarity to patients. These features also lend themselves to the benefits of patient-controlled delivery systems and commercially available devices are described. In this paper we briefly consider the relevant pharmacology of intranasal drug delivery; opioid drugs and formulations; and delivery devices used clinically for intranasal administration. We review the clinical applications of intranasal opioid analgesia. These have included use for in-hospital pain management in adult and paediatric populations, in the emergency department, perioperatively and in burns units. Out-of-hospital use has included palliative care and paramedic use during retrieval and transfer to hospital. Many small trials suggest that intranasal opioids play a useful role in pain management, but large clinical trials are needed to better define advantages, safety and acceptability.

Disposition and clinical outcome after intraperitoneal meperidine and ropivacaine administration during laparoscopic surgery.

BACKGROUND: Limited evidence supports the efficacy of intraperitoneal (IP) meperidine or local anesthetic for postoperative analgesia. Our study aims were to investigate analgesic efficacy and to quantify the plasma concentrations of meperidine and ropivacaine after IP administration. The null hypothesis was that there was no significant difference among groups for dynamic pain in the first 24 h after major abdominal laparoscopic surgery. METHODS: This double-blind, five parallel group, placebo-controlled, two-center trial randomized 250 women having laparoscopic surgery to receive IP meperidine 50 or 100 mg (groups M50 and M100), ropivacaine 150 mg (group R150), meperidine 50 mg and ropivacaine 150 mg (group M50R150), all with intramuscular saline, or IP saline, with intramuscular meperidine 50 mg (group C). The primary outcome was pain during recovery. A pharmacokinetic profile of the drugs was obtained. RESULTS: There were no significant differences among groups for mean (sd) dynamic pain scores in the postoperative care unit (2.2 [2.8], 2.5 [3.3], 1.6 [2.5], 2.6 [3.2], 2.7 [3.2] for groups C, M50, M100, R150, and M50R150, P = 0.50) or thereafter. There were no significant differences among groups for pain scores at rest, IV morphine use, recovery characteristics and patient satisfaction. After IP administration of meperidine 50 mg the plasma concentration (median average 55-60 microg/L) was approximately half that of an equivalent intramuscular dose (median average 113 mug/L). CONCLUSIONS: Compared with systemic opioid, IP meperidine and ropivacaine, alone or in combination, did not produce better pain relief or opioid dose-sparing after laparoscopic surgery.

A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery.

BACKGROUND: Although pregabalin shows efficacy against neuropathic pain, very limited evidence supports postoperative analgesic efficacy. Our study objective was to investigate analgesic efficacy in an ambulatory day surgical population experiencing acute visceral pain. The null hypothesis was that there was no significant difference in pain relief between pregabalin and placebo. METHODS: A randomized, double-blind, parallel-group, placebo-controlled trial was performed in 90 women having minor gynecological surgery involving the uterus. Patients received either oral pregabalin 100 mg (Group PG) or placebo (Group C) approximately 1 h before surgery. The primary outcome was pain score in the recovery unit and patients were followed for 24 h. RESULTS: There was no significant difference between groups for pain experienced in the recovery room (median, interquartile range 16, 0-36 vs 10, 6.5-36 for Groups PG and C, respectively, P = 0.80) or thereafter; nor for recovery room fentanyl requirement (42% Group PG versus 27% Group C, P = 0.12) or the quality of recovery at 24 h postoperatively (median, interquartile range score 17, 17-18 Group PG versus 18, 16.5-18 Group C, P = 0.75). The incidence of posthospital discharge light-headedness, visual disturbance, and difficulty with walking was significantly higher in the pregabalin group. CONCLUSIONS: A single preoperative dose of 100 mg pregabalin does not reduce acute pain or improve recovery after minor surgery involving only the uterus.

Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial.

BACKGROUND: Nitrous oxide is widely used in anesthesia, often administered at an inspired concentration around 70%. Although nitrous oxide interferes with vitamin B12, folate metabolism, and deoxyribonucleic acid synthesis and prevents the use of high inspired oxygen concentrations, the consequences of these effects are unclear. METHODS: Patients having major surgery expected to last at least 2 h were randomly assigned to nitrous oxide-free (80% oxygen, 20% nitrogen) or nitrous oxide-based (70% N2O, 30% oxygen) anesthesia. Patients and observers were blind to group identity. The primary endpoint was duration of hospital stay. Secondary endpoints included duration of intensive care stay and postoperative complications; the latter included severe nausea and vomiting, and the following major complications: pneumonia, pneumothorax, pulmonary embolism, wound infection, myocardial infarction, venous thromboembolism, stroke, awareness, and death within 30 days of surgery. RESULTS: Of 3,187 eligible patients, 2,050 consenting patients were recruited. Patients in the nitrous oxide-free group had significantly lower rates of major complications (odds ratio, 0.71; 95% confidence interval, 0.56-0.89; P = 0.003) and severe nausea and vomiting (odds ratio, 0.40; 95% confidence interval, 0.31-0.51; P < 0.001), but median duration of hospital stay did not differ substantially between groups (7.0 vs. 7.1 days; P = 0.06). Among patients admitted to the intensive care unit postoperatively, those in the nitrous oxide-free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group (hazard ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02). CONCLUSIONS: Avoidance of nitrous oxide and the concomitant increase in inspired oxygen concentration decreases the incidence of complications after major surgery, but does not significantly affect the duration of hospital stay. The routine use of nitrous oxide in patients undergoing major surgery should be questioned.

Ondansetron and dexamethasone dose combinations for prophylaxis against postoperative nausea and vomiting.

BACKGROUND: Patients at high risk of postoperative nausea and vomiting often receive more than one prophylactic antiemetic drug. In this study we sought to determine whether one or more of four dose combinations of dexamethasone and ondansetron was superior in efficacy. METHODS: In a randomized, double-blind trial of four dose combinations, women having day-surgical gynecologic laparoscopy received IV dexamethasone and ondansetron 4 + 4 mg (Group D4/O4, n = 154), 4 + 2 mg (Group D4/O2, n = 151), 2 + 4 mg (Group D2/O4, n = 154), or 2 + 2 mg (Group D2/O2, n = 155). RESULTS: The groups were not significantly different for predicted risk or characteristics. The incidence of vomiting until discharge did not differ significantly (5%, 4%, 9% and 8% for Groups D4/O4, D4/O2, D2/O4 and D2/O2 respectively, P = 0.17), nor were there significant differences among groups in the incidence of vomiting until 24 h postoperatively, no nausea and no vomiting, antiemetic treatment, neither vomiting nor antiemetic treatment (80%-83% across groups), or inpatient satisfaction and recovery scores, or time to discharge. Average nausea scores were low in all groups, but the incidence of nausea until 24 h postoperatively was significantly higher among groups receiving only 2 mg of dexamethasone (P < 0.03). CONCLUSIONS: All combinations were associated with a low incidence of vomiting and rescue treatment, with dexamethasone 2 mg plus ondansetron 2 mg not significantly different to other dose combinations except that groups receiving 2 mg dexamethasone had a more frequent incidence of nausea.

Dreaming during anesthesia and anesthetic depth in elective surgery patients: a prospective cohort study.

BACKGROUND: Dreaming reported after anesthesia remains a poorly understood phenomenon. Dreaming may be related to light anesthesia and represent near-miss awareness. However, few studies have assessed the relation between dreaming and depth of anesthesia, and their results were inconclusive. Therefore, the authors tested the hypothesis that dreaming during anesthesia is associated with light anesthesia, as evidenced by higher Bispectral Index values during maintenance of anesthesia. METHODS: With approval, 300 consenting healthy patients, aged 18-50 yr, presenting for elective surgery requiring relaxant general anesthesia with a broad range of agents were studied. Patients were interviewed on emergence and 2-4 h postoperatively. The Bispectral Index was recorded from induction until the first interview. Dream content and form were also assessed. RESULTS: Dreaming was reported by 22% of patients on emergence. There was no difference between dreamers and nondreamers in median Bispectral Index values during maintenance (37 [23-55] vs. 38 [20-59]; P=0.68) or the time at Bispectral Index values greater than 60 (0 [0-7] vs. 0 [0-31] min; P=0.38). Dreamers tended to be younger and male, to have high home dream recall, to receive propofol maintenance or regional anesthesia, and to open their eyes sooner after surgery. Most dreams were similar to dreams of sleep and were pleasant, and the content was unrelated to surgery. CONCLUSIONS: Dreaming during anesthesia is unrelated to the depth of anesthesia in almost all cases. Similarities with dreams of sleep suggest that anesthetic dreaming occurs during recovery, when patients are sedated or in a physiologic sleep state.

Neuraxial drug administration: a review of treatment options for anaesthesia and analgesia.

Neuraxial drug administration describes techniques that deliver drugs in close proximity to the spinal cord, i.e. intrathecally into the CSF or epidurally into the fatty tissues surrounding the dura, by injection or infusion. This approach was initially developed in the form of spinal anaesthesia over 100 years ago. Since then, neuraxial drug administration has evolved and now includes a wide range of techniques to administer a large number of different drugs to provide anaesthesia, but also analgesia and treatment of spasticity in a variety of acute and chronic settings. This review concentrates on the pharmacological agents used and the clinical basis behind currently utilised approaches to neuraxial drug administration. With regard to local anaesthetics, the main focus is on the development of the enantiomer-specific compounds ropivacaine and levobupivacaine, which provide similar efficacy to bupivacaine with a reduced risk of severe cardiotoxicity. Opioids are the other group of drugs widely used neuraxially, in particular to provide analgesia alone or more commonly in combination with other agents. The physicochemical properties of the various opioids explain the main differences in efficacy and safety between these drugs when used intrathecally, of which morphine, fentanyl and sufentanil are most commonly used. Another group of drugs including clonidine, dexmedetomidine and epinephrine (adrenaline) provide neuraxial analgesia via alpha-adrenergic receptors and are used mainly as adjuvants to local anaesthetics and opioids. Furthermore, intrathecal baclofen is in routine clinical use to treat spasticity in a number of neurological conditions. Beside these established approaches, a wide range of other drugs have been assessed for neuraxial administration to provide analgesia; however, most are in various early stages of investigation and are not used routinely. These drugs include neostigmine, ketamine, midazolam and adenosine, and the conotoxin ziconotide. The latter is possibly the most unusual compound here; it has recently gained registration for intrathecal use in specific chronic pain conditions.