Mark W. Crawford

Development of Acute Opioid Tolerance During Infusion of Remifentanil for Pediatric Scoliosis Surgery

We tested the hypothesis that continuous intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery. Thirty adolescents were randomly assigned to receive an intraoperative analgesic regimen consisting of continuous remifentanil infusion or intermittent morphine alone. Postoperative analgesic consumption was assessed with a patient-controlled analgesia device that was used to self-administer morphine. Cumulative postoperative morphine consumption, pain scores, and sedation scores were recorded by a blinded investigator every hour for the first 4 h postoperatively and then every 4 h for a total of 24 h. Cumulative morphine consumption in the remifentanil group was significantly more than that in the morphine group at each time point in the initial 24 h after surgery (P < 0.0001). At 24 h after surgery, cumulative morphine consumption was 30% greater in the remifentanil group (1.65 ± 0.41 mg/kg) than in the morphine group (1.27 ± 0.32 mg/kg) (95% confidence interval for the difference, 0.11 to 0.65 mg/kg). Differences in pain and sedation scores were not statistically significant. These data suggest that intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery.

Hemodynamic and Organ Blood Flow Responses to Halothane and Sevoflurane Anesthesia During Spontaneous Ventilation

This study compared systemic hemodynamic and organ blood flow responses to equipotent concentrations of halothane and sevoflurane during spontaneous ventilation in the rat. The MAC values for halothane and sevoflurane were determined. Cardiac output and organ blood flows were measured using radiolabeled microspheres. Measurements were obtained in awake rats (control values) and at 1.0 MAC halothane or sevoflurane. The MAC values (mean ± SEM) for halothane and sevoflurane were 1.10% ± 0.05% and 2.40% ± 0.05%, respectively. The Paco2increased to a similar extent in both groups compared with control values. During halothane anesthesia, heart rate decreased by 12% (P < 0.01), cardiac index by 26% (P < 0.01), and mean arterial blood pressure by 18% (P < 0.01) compared with control values. Stroke volume index and systemic vascular resistance did not change. During sevoflurane anesthesia, hemodynamic variables remained unchanged compared with control values. Coronary blood flow decreased by 21% (P < 0.01) and renal blood flow by 18% (P < 0.01) at 1.0 MAC halothane, whereas both remained unchanged at 1.0 MAC sevoflurane. Cerebral blood flow increased to a greater extent with halothane (63%; P < 0.01) than with sevoflurane (35%; P < 0.05). During halothane anesthesia, hepatic arterial blood flow increased by 48% (P < 0.01), whereas portal tributary blood flow decreased by 28% (P < 0.01). During sevoflurane anesthesia, hepatic arterial blood flow increased by 70% (P < 0.01) without a concomitant reduction in portal tributary blood flow. Total liver blood flow decreased only with halothane (16%; P < 0.05). In conclusion, for comparable increases in Paco2, systemic hemodynamic and organ blood flow responses to halothane are significantly greater than the responses to sevoflurane at an equipotent concentration of 1.0 MAC in the spontaneously ventilating rat.

Additive contribution of nitrous oxide to sevoflurane minimum alveolar concentration for tracheal intubation in children

BACKGROUND To study the interaction between nitrous oxide and sevoflurane during trachea intubation, the authors determined the minimum alveolar concentration of sevoflurane for tracheal intubation (MAC(TI)) with and without nitrous oxide in children. METHODS Seventy-two children aged 1-7 yr were assigned randomly to receive one of three end-tidal concentrations of nitrous oxide and one of four end-tidal concentrations of sevoflurane: 0% nitrous oxide with 2.0, 2.5, 3.0, or 3.5% sevoflurane: 33% nitrous oxide with 1.5, 2.0, 2.5, or 3.0% sevoflurane; or 66% nitrous oxide with 1.0, 1.5, 2.0, or 2.5% sevoflurane. After steady state end-tidal anesthetic concentrations were maintained for at least 10 min, laryngoscopy and intubation were attempted using a straight-blade laryngoscope and an uncuffed tracheal tube. The interaction between nitrous oxide and sevoflurane was investigated using logistic regression analysis of the responses to intubation. RESULTS Logistic regression curves of the probability of no movement in response to intubation in the presence of sevoflurane and 0, 33, and 66% nitrous oxide were parallel. The interaction coefficient between nitrous oxide and sevoflurane did not differ significantly from zero (P = 0.89) and was removed from the logistic model. The MAC(TI) (+/- SE) of sevoflurane was 2.66+/-0.16%, and the concentration of sevoflurane required to prevent movement in 95% of children was 3.54+/-0.25%. Thirty-three percent and 66% nitrous oxide decreased the MAC(TI) of sevoflurane by 18% and 40% (P<0.001), respectively. CONCLUSIONS We conclude that nitrous oxide and sevoflurane suppress the responses to tracheal intubation in a linear and additive fashion in children.

Effects of duration of fasting on gastric fluid pH and volume in healthy children

To determine the effects of duration of fasting before elective surgery on gastric fluid pH and volume in children, a prospective, randomized, blinded study of 100 unpremedicated children, aged 1–14 yr, was undertaken. Each child was given 2 mL/kg of water orally and then fasted 2, 4, or 6 h preoperatively. After induction of anesthesia and tracheal intubation, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube. Gastric fluid pH was measured using a calibrated PHM62 radiometer. Gastric fluid volume was the total volume of fluid aspirated from the stomach. The duration of fasting was between 2.0 and 8.5 h. We found that neither gastric fluid pH nor gastric fluid volume correlated with the duration of fasting. The mean (± SD) gastric fluid pH was 1.80 ± 0.79 and the mean (± SD) gastric fluid volume was 0.56 ± 0.39 mL/kg. Gastric fluid pH was >2.5 and volume >0.4 mL/kg in 53% of children. We conclude that healthy children may receive 2 mL/kg of water up to 2 h before elective surgery without decreasing gastric fluid pH or increasing gastric fluid volume beyond values obtained after fasting for 6 h.

Dose-response of remifentanil for tracheal intubation in infants

To compare the dose-response of remifentanil for tracheal intubation in infants and children, 32 healthy full-term infants and 32 children were anesthetized with 10 &mgr;g/kg glycopyrrolate and 4.0 mg/kg propofol and administered 1 of 4 doses of remifentanil (1.25, 1.50, 1.75, or 2.00 &mgr;g/kg) to facilitate tracheal intubation. We determined the effective doses of remifentanil in 50% (ED50) and 98% (ED98) of patients by using logistic regression analysis. We found that logistic regression curves were similar for infants and children (P = 0.38). ED50 and ED98 values for remifentanil were 1.70 ± 0.1 &mgr;g/kg and 2.88 ± 0.5 &mgr;g/kg, respectively. In a second double-blind study, 24 infants were anesthetized with propofol and randomized to receive either 3.0 &mgr;g/kg remifentanil or 2.0 mg/kg succinylcholine to facilitate tracheal intubation. The duration of apnea, tracheal intubating conditions and hemodynamic changes were determined. We found that the duration of apnea and intubating conditions after propofol/remifentanil were similar to those after propofol/succinylcholine. Bradycardia, hypotension, and chest wall rigidity did not occur. We conclude that the dose-response of remifentanil for tracheal intubation is similar in infants and children. Propofol/remifentanil provides clinically acceptable intubating conditions, stable hemodynamics, and a duration of apnea comparable to that with propofol/succinylcholine in infants.

Effect of increasing depth of propofol anesthesia on upper airway configuration in children

Background The upper airway tends to be obstructed during anesthesia in spontaneously breathing patients. The purpose of the current study was to determine the effect of increasing depth of propofol anesthesia on airway size and configuration in children. Methods Magnetic resonance images of the upper airway were obtained in 15 children, aged 2–6 yr. Cross-sectional area, anteroposterior dimension, and transverse dimension were measured at the level of the soft palate, dorsum of the tongue, and tip of the epiglottis. Images were obtained during infusion of propofol at a rate of 50–80 &mgr;g · kg−1 · min−1 and after increasing the depth of anesthesia by administering a bolus dose of propofol and increasing the infusion rate to 240 &mgr;g · kg−1 · min−1. Results Overall, the cross-sectional area of the entire pharyngeal airway decreased with increasing depth of anesthesia. The reduction in cross-sectional area was greatest at the level of the epiglottis (24.5 mm2, 95% confidence interval = 16.9–32.2 mm2; P < 0.0001), intermediate at the level of the tongue (19.3 mm2, 95% confidence interval = 9.2–29.3 mm2; P < 0.0001), and least at the level of the soft palate (12.6 mm2, 95% confidence interval = 2.7–22.6 mm2; P < 0.005) in expiration and resulted predominantly from a reduction in anteroposterior dimension. The airway cross-sectional area decreased further in inspiration at the level of the epiglottis. The narrowest portion of the airway resided at the level of the soft palate or epiglottis in the majority of children. Conclusion Increasing depth of propofol anesthesia in children is associated with upper airway narrowing that occurs throughout the entire upper airway and is most pronounced in the hypopharynx at the level of the epiglottis.

Intraoperative low-dose ketamine does not prevent a remifentanil-induced increase in morphine requirement after pediatric scoliosis surgery.

BACKGROUND: Remifentanil-based anesthesia is commonly used to facilitate neurophysiologic monitoring during pediatric scoliosis surgery. Acute opioid tolerance and/or hyperalgesia resulting from remifentanil-based anesthesia may involve activation of N-methyl-d-aspartate systems. We hypothesized that low-dose intraoperative infusion of the N-methyl-d-aspartate antagonist ketamine would suppress the development of tolerance and thereby decrease postoperative morphine consumption in children receiving remifentanil-based anesthesia for scoliosis surgery. METHODS: Thirty-four adolescents aged 12–18 yr scheduled for scoliosis surgery were randomly assigned to receive intraoperative low-dose ketamine (bolus dose of 0.5 mg/kg followed by continuous infusion of 4 &mgr;g · kg−1 · min−1) or an equal volume of saline during propofol/remifentanil anesthesia. Cumulative morphine consumption was assessed using a patient-controlled analgesia device for 72 h after surgery. Postoperative morphine consumption, pain scores at rest and during cough, and sedation scores were recorded by a blinded investigator every hour for the first 4 h, every 4 hours for 20 h, and then every 12 hours for 72 h. RESULTS: Cumulative morphine consumption at 24, 48, and 72 h after surgery did not differ significantly between groups (ketamine group: 1.57 ± 0.56, 3.05 ± 1.14, and 4.46 ± 1.53 mg/kg; saline group: 1.60 ± 0.53, 2.87 ± 1.05, and 4.11 ± 1.71 mg/kg, respectively). No differences in pain or sedation scores were found. The duration of anesthesia was similar in the two groups. CONCLUSIONS: These data do not support the use of intraoperative low-dose ketamine to prevent the development of remifentanil-induced acute opioid tolerance and/or hyperalgesia during pediatric scoliosis surgery.

Effect of propofol infusion on splanchnic hemodynamics and liver oxygen consumption in the rat : a dose-response study

BackgroundPropofol has been used for the maintenance of anesthesia. The effects of propofol infusion on splanchnic hemodynamics and liver oxygen consumption, however, have not been reported. In the current investigation, the authors studied the effects of a continuous infusion of propofol on systemic and splanchnic hemodynamics using a new method to measure liver oxygen consumption in awake control and anesthetized rats. MethodsCannulas were inserted into the left ventricle, femorla artery, portal vein, and hepatic vein during ether anesthesia, and the rats were allowed to awaken and recover for 3–4 h before study. Animals were infused for 30 min with either saline (controls) or propofol at a rate of 300, 600, 900, or 1,200 μg.kg-1·min-1. Cardiac output and organ blood flows were measured using radiolabelled microspheres, and blood samples from the femoral artery, portal vein, and hepatic vein were used to determine liver oxygen consumption. ResultsMean arterial pressure decreased in a dose-dependent manner with a 25% reduction at the highest infusion rate. Systemic vascular resistance similarly decreased, whereas cardiac output remained unchanged at all the infusion rates. Hepatic arterial blood flow increased in a dose-dependent fashion over the dose range studied, to a maximum increase of 120%. Portal tributary blood flow increased by 30% at the highest infusion rate. Total liver blood flow increased in a dose-dependent manner to a maximum of 38%. Total oxygen delivery to the liver by the hepatic artery and portal vein increased in a dose-dependent fashion to a maximum increase of 51% at an infusion rate of 1,200 μg·kg-1·min-1. The percent of oxygen extracted by the liver was not altered by propofol infusion, and hepatic venous oxygen saturation did not decrease at any dose studied. Coronary and renal blood flows were not altered. Arterial Paco2 increased from 31 ± 2 mmHg in awake control rats to 41 ± 2 mmHg in spontaneously breathing rats infused with 1,200 μ·kg-1·min-1 propofol. ConclusionsThe maintenance of anesthesia using an infusion of propofol resulted in an increase in liver oxygen consumption that was fully compensated for by an increase in oxygen delivery to the liver. Splanchnic hemodynamics and liver oxygenation are not adversely affected during maintenance of anesthesia with propofol in the normal rat.

A Population-based Study Evaluating the Association between Surgery in Early Life and Child Development at Primary School Entry

Background:It is unclear whether exposure to surgery in early life has long-term adverse effects on child development. The authors aimed to investigate whether surgery in early childhood is associated with adverse effects on child development measured at primary school entry. Methods:The authors conducted a population-based cohort study in Ontario, Canada, by linking provincial health administrative databases to children’s developmental outcomes measured by the Early Development Instrument (EDI). From a cohort of 188,557 children, 28,366 children who underwent surgery before EDI completion (age 5 to 6 yr) were matched to 55,910 unexposed children. The primary outcome was early developmental vulnerability, defined as any domain of the EDI in the lowest tenth percentile of the population. Subgroup analyses were performed based on age at first surgery (less than 2 and greater than or equal to 2 yr) and frequency of surgery. Results:Early developmental vulnerability was increased in the exposed group (7,259/28,366; 25.6%) compared with the unexposed group (13,957/55,910; 25.0%), adjusted odds ratio, 1.05; 95% CI, 1.01 to 1.08. Children aged greater than or equal to 2 yr at the time of first surgery had increased odds of early developmental vulnerability compared with unexposed children (odds ratio, 1.05; 95% CI, 1.01 to 1.10), but children aged less than 2 yr at the time of first exposure were not at increased risk (odds ratio, 1.04; 95% CI, 0.98 to 1.10). There was no increase in odds of early developmental vulnerability with increasing frequency of exposure. Conclusions:Children who undergo surgery before primary school age are at increased risk of early developmental vulnerability, but the magnitude of the difference between exposed and unexposed children is small.

A pilot study of the rectus sheath block for pain control after umbilical hernia repair

Background : Umbilical hernia repair, a common day surgery procedure in children, is associated with significant postoperative discomfort. The rectus sheath block may offer improved pain management following umbilical hernia repair. In this pilot study, we compared the efficacy of the rectus sheath block with that of our current standard practice – local anesthetic infiltration into the surgical wound – for pain control after umbilical hernia repair in children.