Nathan Pace - Academia.edu (original) (raw)

Papers by Nathan Pace

BMJ, 2011

Objective To systematically determine the most efficacious approach for preventing pain on inject... more Objective To systematically determine the most efficacious approach for preventing pain on injection of propofol. Design Systematic review and meta-analysis. Data sources PubMed, Embase, Cochrane Library, www.clinicaltrials.gov, and hand searching from the reference lists of identified papers. Study selection Randomised controlled trials comparing drug and non-drug interventions with placebo or another intervention to alleviate pain on injection of propofol in adults. Results Data were analysed from 177 randomised controlled trials totalling 25 260 adults. The overall risk of pain from propofol injection alone was about 60%. Using an antecubital vein instead of a hand vein was the most effective single intervention (relative risk 0.14, 95% confidence interval 0.07 to 0.30). Pretreatment using lidocaine (lignocaine) in conjunction with venous occlusion was similarly effective (0.29, 0.22 to 0.38). Other effective interventions were a lidocaine-propofol admixture (0.40, 0.33 to 0.48); pretreatment with lidocaine (0.47, 0.40 to 0.56), opioids (0.49, 0.41 to 0.59), ketamine (0.52, 0.46 to 0.57), or non-steroidal anti-inflammatory drugs (0.67, 0.49 to 0.91); and propofol emulsions containing medium and long chain triglycerides (0.75, 0.67 to 0.84). Statistical testing of indirect comparisons showed that use of the antecubital vein and pretreatment using lidocaine along with venous occlusion to be more efficacious than the other interventions. Conclusions The two most efficacious interventions to reduce pain on injection of propofol were use of the antecubital vein, or pretreatment using lidocaine in conjunction with venous occlusion when the hand vein was chosen. Under the assumption of independent efficacy a third practical alternative could be pretreatment of the hand vein with lidocaine or ketamine and use of a propofol emulsion containing medium and long chain triglycerides. Although not the most effective intervention on its own, a small dose of opioids before induction halved the risk of pain from the injection and thus can generally be recommended unless contraindicated.

The classification system that tracks patients level of consciousness during anesthesia and surge... more The classification system that tracks patients level of consciousness during anesthesia and surgery. Grades 0 to 5 were assigned to each of the 160 included RCTs

Different IV techniques were compared to IV techniques and volatile techniques and other techniqu... more Different IV techniques were compared to IV techniques and volatile techniques and other techniques. Inadequate anesthesia protocol are summarized from some of the RCTs

An analysis by the expert peer reviewer #2 and expert coauthor, MaW, of our classification system

BACKGROUND: General anaesthesia is usually associated with unconsciousness. 'Awareness' i... more BACKGROUND: General anaesthesia is usually associated with unconsciousness. 'Awareness' is when patients have postoperative recall of events or experiences during surgery. 'Wakefulness' is when patients become conscious during surgery, but have no postoperative recollection of the period of consciousness. OBJECTIVES: To evaluate the efficacy of two types of anaesthetic interventions in reducing clinically significant awareness: - anaesthetic drug regimens; and - intraoperative anaesthetic depth monitors. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, ISSUE 4 2016); PubMed from 1950 to April 2016; MEDLINE from 1950 to April 2016; and Embase from 1980 to April 2016. We contacted experts to identify additional studies. We performed a handsearch of the citations in the review. We did not search trial registries. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of either anaesthetic regimens or anaesthetic depth monitors. We excluded volunteer studies, studies of patients prior to skin incision, intensive care unit studies, and studies that only randomized different word presentations for memory tests (not anaesthetic interventions). Anaesthetic drug regimens included studies of induction or maintenance, or both. Anaesthetic depth monitors included the Bispectral Index monitor, M-Entropy, Narcotrend monitor, cerebral function monitor, cerebral state monitor, patient state index, and lower oesophageal contractility monitor. The use of anaesthetic depth monitors allows the titration of anaesthetic drugs to maintain unconsciousness. DATA COLLECTION AND ANALYSIS: At least two authors independently scanned abstracts, extracted data from the studies, and evaluated studies for risk of bias. We made attempts to contact all authors for additional clarification. We performed meta-analysis statistics in packages of the R language. MAIN RESULTS: We included 160 studies with 54,109 enrolled participants; 53,713 participants started the studies and 50,034 completed the studies or data analysis (or both). We could not use 115 RCTs in meta-analytic comparisons because they had zero awareness events. We did not merge 27 of the remaining 45 studies because they had excessive clinical and methodological heterogeneity. We pooled the remaining 18 eligible RCTs in meta-analysis. There are 10 studies awaiting classification which we will process when we update the review. The meta-analyses included 18 trials with 36,034 participants. In the analysis of anaesthetic depth monitoring (either Bispectral Index or M-entropy) versus standard clinical and electronic monitoring, there were nine trials with 34,744 participants. The overall event rate was 0.5%. The effect favoured neither anaesthetic depth monitoring nor standard clinical and electronic monitoring, with little precision in the odds ratio (OR) estimate (OR 0.98, 95% confidence interval (CI) 0.59 to 1.62). In a five-study subset of Bispectral Index monitoring versus standard clinical and electronic monitoring, with 34,181 participants, 503 participants gave awareness reports to a blinded, expert panel who adjudicated or judged the outcome for each patient after reviewing the questionnaires: no awareness, possible awareness, or definite awareness. Experts judged 351 patient awareness reports to have no awareness, 87 to have possible awareness, and 65 to have definite awareness. The effect size favoured neither Bispectral Index monitoring nor standard clinical and electronic monitoring, with little precision in the OR estimate for the combination of definite and possible awareness (OR 0.96, 95% CI 0.35 to 2.65). The effect size favoured Bispectral Index monitoring for definite awareness, but with little precision in the OR estimate (OR 0.60, 95% CI 0.13 to 2.75). We performed three smaller meta-analyses of anaesthetic drugs. There were nine studies with 1290 participants. Wakefulness was reduced by ketamine and etomidate compared to thiopental. Wakefulness was more frequent than awareness. Benzodiazepines reduces awareness compared to thiopental, ketamine, and placebo., Also, higher doses of inhaled anaesthetics versus lower doses reduced the risk of awareness. We graded the quality of the evidence as low or very low in the 'Summary of findings' tables for the five comparisons. Most of the secondary outcomes in this review were not reported in the included RCTs. AUTHORS' CONCLUSIONS: Anaesthetic depth monitors may have similar effects to standard clinical and electrical monitoring on the risk of awareness during surgery. In older studies comparing anaesthetics in a smaller portion of the patient sample, wakefulness occurred more frequently than awareness. Use of etomidate and ketamine lowered the risk of wakefulness compared to thiopental. Benzodiazepines compared to thiopental and ketamine, or higher doses of inhaled anaesthetics versus lower doses, reduced the risk of awareness. PLAIN LANGUAGE SUMMARY: Methods to…

British journal of anaesthesia, 2018

Maximising patient comfort during and after surgery is a primary concern of anaesthetists and oth... more Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: p...

Respiratory Care, 2017

BACKGROUND: Research has shown that increased breathing frequency during cardiopulmonary resuscit... more BACKGROUND: Research has shown that increased breathing frequency during cardiopulmonary resuscitation is inversely correlated with systolic blood pressure. Rescuers often hyperventilate during cardiopulmonary resuscitation (CPR). Current American Heart Association advanced cardiac life support recommends a ventilation rate of 8-10 breaths/min. We hypothesized that a small, turbine-driven ventilator would allow rescuers to adhere more closely to advanced cardiac life support (ACLS) guidelines. METHODS: Twenty-four ACLS-certified health-care professionals were paired into groups of 2. Each team performed 4 randomized rounds of 2-min cycles of CPR on an intubated mannikin, with individuals altering between compressions and breaths. Two rounds of CPR were performed with a self-inflating bag, and 2 rounds were with the ventilator. The ventilator was set to deliver 8 breaths/min, pressure limit 22 cm H 2 O. Frequency, tidal volume (V T), peak inspiratory pressure, and compression interruptions (hands-off time) were recorded. Data were analyzed with a linear mixed model and Welch 2-sample t test. RESULTS: The median (interquartile range [IQR]) frequency with the ventilator was 7.98 (7.98-7.99) breaths/min. Median (IQR) frequency with the self-inflating bag was 9.5 (8.2-10.7) breaths/min. Median (IQR) ventilator V T was 0.5 (0.5-0.5) L. Median (IQR) self-inflating bag V T was 0.6 (0.5-0.7) L. Median (IQR) ventilator peak inspiratory pressure was 22 (22-22) cm H 2 O. Median (IQR) self-inflating bag peak inspiratory pressure was 30 (27-35) cm H 2 O. Mean ؎ SD hands-off times for ventilator and selfinflating bag were 5.25 ؎ 2.11 and 6.41 ؎ 1.45 s, respectively. CONCLUSIONS: When compared with a ventilator, volunteers ventilated with a self-inflating bag within ACLS guidelines. However, volunteers ventilated with increased variation, at higher V T levels, and at higher peak pressures with the self-inflating bag. Hands-off time was also significantly lower with the ventilator. (Clini-calTrials.gov registration NCT02743299.

Respiratory care, 2008

Anatomic dead space (also called airway or tracheal dead space) is the part of the tidal volume t... more Anatomic dead space (also called airway or tracheal dead space) is the part of the tidal volume that does not participate in gas exchange. Some contemporary ventilation protocols, such as the Acute Respiratory Distress Syndrome Network protocol, call for smaller tidal volumes than were traditionally delivered. With smaller tidal volumes, the percentage of each delivered breath that is wasted in the anatomic dead space is greater than it is with larger tidal volumes. Many respiratory and medical textbooks state that anatomic dead space can be estimated from the patient's weight by assuming there is approximately 1 mL of dead space for every pound of body weight. With a volumetric capnography monitor that measures on-airway flow and CO2, the anatomic dead space can be automatically and directly measured with the Fowler method, in which dead space equals the exhaled volume up to the point when CO2 rises above a threshold. We analyzed data from 58 patients (43 male, 15 female) to as...

Cochrane Database of Systematic Reviews, 2014

CT angiography criteria used to review CT images. Computed tomography (CT) angiography for confir... more CT angiography criteria used to review CT images. Computed tomography (CT) angiography for confirmation of the clinical diagnosis of brain death (Review)

New England Journal of Medicine, 2000

Background Intrathecal administration of morphine produces intense analgesia, but it depresses re... more Background Intrathecal administration of morphine produces intense analgesia, but it depresses respiration, an effect that can be life-threatening. Whether intrathecal morphine affects the ventilatory response to hypoxia, however, is not known. Methods We randomly assigned 30 men to receive one of three study treatments in a double-blind fashion: intravenous morphine (0.14 mg per kilogram of body weight) with intrathecal placebo; intrathecal morphine (0.3 mg) with intravenous placebo; or intravenous and intrathecal placebo. The selected doses of intravenous and intrathecal morphine produce similar degrees of analgesia. The ventilatory response to hypercapnia, the subsequent response to acute hypoxia during hypercapnic breathing (targeted end-tidal partial pressures of expired oxygen and carbon dioxide, 45 mm Hg), and the plasma levels of morphine and morphine metabolites were measured at base line (before drug administration) and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration.

British Journal of Anaesthesia, 2010

Background. The aim of this study was to determine whether the ED 50 dose of bupivacaine 0.5% for... more Background. The aim of this study was to determine whether the ED 50 dose of bupivacaine 0.5% for supraclavicular brachial plexus block increases with increasing body mass index (BMI). Methods. This double-blind, non-randomized trial followed an up-and-down sequential allocation design. Adult patients undergoing elective upper limb surgery under ultrasound-guided supraclavicular brachial block were recruited. A preliminary study was used to guide the dosing schedule for the main study in which patients were divided into three groups according to their BMI (Group A, BMI .27 kg m 22 ; Group B, BMI 24-27 kg m 22 ; Group C, BMI ,24 kg m 22). The study design and analysis followed Dixon's small sample model using a 'nominal' sample size of six per group. Results. Twenty-one patients were recruited to the preliminary study. Using isotonic regression, the ED 50 for bupivacaine 0.5% was estimated to be 8.9 ml [95% confidence interval (CI) 7.8-15.9]. In comparison, the ED 50 volume was found to be 10.8 ml (95% CI 5.9-19.7) using the Dixon-Massey formula. In the main study, six patients were recruited in each group with mean (range)

Anesthesiology, 1998

Background The pharmacokinetics of a single dose (15 microg/kg) of oral transmucosal fentanyl cit... more Background The pharmacokinetics of a single dose (15 microg/kg) of oral transmucosal fentanyl citrate (OTFC) have been characterized. A range of doses may eventually be used in clinical practice. The goal of this study was to determine if the pharmacokinetics of OTFC are dose proportional for doses ranging from 200 to 1,600 microg. Methods Twelve healthy male volunteers were studied on four different occasions, receiving 200, 400, 800, and 1,600 microg OTFC in a double-blind, randomized protocol. Venous blood samples were collected at selected times during and after dosing for a 24-h period and assayed for fentanyl using a radioimmunoassay. Maximum concentration, time to maximum concentration, area under the curve, and elimination half-life were determined for each dose administered. In addition, respiratory rate, need for verbal prompting to breathe, and supplemental oxygen requirements were noted. Results Mean fentanyl concentration time curves were similarly shaped with increasin...

Anesthesiology, 2006

Background Combining a hypnotic and an analgesic to produce sedation, analgesia, and surgical imm... more Background Combining a hypnotic and an analgesic to produce sedation, analgesia, and surgical immobility required for clinical anesthesia is more common than administration of a volatile anesthetic alone. The aim of this study was to apply response surface methods to characterize the interactions between remifentanil and sevoflurane. Methods Sixteen adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the Observer's Assessment of Alertness/Sedation score and response to a series of randomly applied experimental pain stimuli (pressure algometry, electrical tetany, and thermal stimulation) were observed for each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for sedation and analgesic endpoints. Using computer simulation, the pharmacodynamic interaction models were c...

Anesthesiology, 2007

Background Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Pr... more Background Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Previous studies have shown that opioids reduce the clinical requirements of sedatives needed to provide adequate anesthesia. Processed electroencephalographic parameters, such as the Bispectral Index (BIS; Aspect Medical Systems, Newton, MA) and Auditory Evoked Potential Index (AAI; Alaris Medical Systems, San Diego, CA), can be used intraoperatively to assess the depth of sedation. The aim of this study was to characterize how the addition of opioids sufficient to change the clinical level of sedation influenced the BIS and AAI. Methods Twenty-four adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the modified Observer's Assessment of Alertness/Sedation score, BIS, and AAI were measured at each target concentration pair. Response ...

Anesthesiology, 2000

Background Oral transmucosal fentanyl citrate (OTFC) is a solid form of fentanyl that delivers th... more Background Oral transmucosal fentanyl citrate (OTFC) is a solid form of fentanyl that delivers the drug through the oral mucosa. The clinical utility of multiple doses of OTFC in the treatment of "breakthrough" cancer pain is under evaluation. The aim of this study was to test the hypothesis that the pharmacokinetics of OTFC do not change with multiple dosing. Methods Twelve healthy adult volunteers received intravenous fentanyl (15 microg/kg) or OTFC (three consecutive doses of 800 microg) on separate study sessions. Arterial blood samples were collected for determination of fentanyl plasma concentration by radioimmunoassay. The descriptive pharmacokinetic parameters (maximum concentration, minimum concentration, and time to maximum concentration) were identified from the raw data and subjected to a nonparametric analysis of variance. Population pharmacokinetic models for all subjects and separate models for each subject were developed to estimate the pharmacokinetic para...

Anesthesiology, 2008

Background Part task training (PTT) focuses on dividing complex tasks into components followed by... more Background Part task training (PTT) focuses on dividing complex tasks into components followed by intensive concentrated training on individual components. Variable priority training (VPT) focuses on optimal distribution of attention when performing multiple tasks simultaneously with the goal of flexible allocation of attention. This study explored how principles of PTT and VPT adapted to anesthesia training would improve first-year anesthesiology residents' management of simulated adverse airway and respiratory events. The authors hypothesized that participants with PTT and VPT would perform better than those with standard training. Methods Twenty-two first-year anesthesia residents were randomly divided into two groups and trained over 12 months. The control group received standard didactic and simulation-based training. The experimental group received similar training but with emphasis on PTT and VPT techniques. Participant ability to manage seven adverse airway and respirato...