David O. Warner

Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort

Background:Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and the development of reading, written language, and math learning disabilities (LD). Methods:This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota, from 1976 to 1982 and who remained in the community at 5 yr of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, sex, and birth weight. Results:Of the 5,357 children in this cohort, 593 received general anesthesia before age 4 yr. Compared with those not receiving anesthesia (n = 4,764), a single exposure to anesthesia (n = 449) was not associated with an increased risk of LD (hazard ratio = 1.0; 95% confidence interval, 0.79–1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for LD (hazard ratio = 1.59; 95% confidence interval, 1.06–2.37, and hazard ratio = 2.60; 95% confidence interval, 1.60–4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P = 0.016). Conclusion:Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. These data cannot reveal whether anesthesia itself may contribute to LD or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.

Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

BACKGROUND: Annually, millions of children are exposed to anesthetic agents that cause apoptotic neurodegeneration in immature animals. To explore the possible significance of these findings in children, we investigated the association between exposure to anesthesia and subsequent (1) learning disabilities (LDs), (2) receipt of an individualized education program for an emotional/behavior disorder (IEP-EBD), and (3) scores of group-administered achievement tests. METHODS: This was a matched cohort study in which children (N = 8548) born between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the source of cases and controls. Those exposed to anesthesia (n = 350) before the age of 2 were matched to unexposed controls (n = 700) on the basis of known risk factors for LDs. Multivariable analysis adjusted for the burden of illness, and outcomes including LDs, receipt of an IEP-EBD, and the results of group-administered tests of cognition and achievement were outcomes. RESULTS: Exposure to multiple, but not single, anesthetic/surgery significantly increased the risk of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26–3.54]), even when accounting for health status. A similar pattern was observed for decrements in group-administered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program. CONCLUSIONS: Repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs but not the need for educational interventions related to emotion/behavior. We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequence.

Preventing postoperative pulmonary complications: the role of the anesthesiologist.

THE Confederate General “Stonewall” Jackson was one of the earliest known victims of a respiratory complication after surgery, dying of pneumonia 10 days after an otherwise successful ether anesthetic in 1863. Despite subsequent advances in anesthesia and surgical care, postoperative pulmonary complications (PPCs) still are a significant problem in modern practice. This commentary examines why PPCs occur and how the anesthesiologist can help prevent them.

Nitric oxide contributes to the rise in forearm blood flow during mental stress in humans.

1. Our aim was to determine whether the vasodilating substance nitric oxide (NO) contributes to the rise in forearm blood flow observed during mental stress in humans. We also determined whether the NO might be released as a result of cholinergic stimulation of the vascular endothelium. 2. Blood flow was measured in both forearms using plethysmography during several 3‐5 min bouts of a colour word test. In one forearm the nitric oxide synthase blocker NG‐monomethyl‐L‐arginine (L‐NMMA) and other drugs were infused via a brachial artery catheter. The contralateral forearm served as a control. 3. When L‐NMMA was given prior to mental stress it blunted the rise in blood flow in the treated forearm almost completely. The normal blood flow response returned during a second bout of stress conducted after a wash‐out period. During a third bout of mental stress, administration of more L‐NMMA again blunted the blood flow responses to mental stress. 4. When atropine was given prior to mental stress, the increases in blood flow were reduced in the treated forearm. Subsequent administration of both atropine and L‐NMMA caused a somewhat greater reduction in the blood flow responses than those observed with atropine alone. 5. These data demonstrate that NO plays a role in forearm vasodilatation during mental stress in humans. It is likely that most of the NO is released by cholinergic stimulation of the vascular endothelium.

Perioperative Pulmonary aspiration in infants and children

BACKGROUND Pulmonary aspiration of gastric contents during the perioperative period in infants and children may be associated with postoperative mortality or pulmonary morbidity. There has not been a recent determination of the frequency of this event and its outcomes in infants and children. METHODS The authors prospectively identified all cases of pulmonary aspiration of gastric contents during the perioperative courses of 56,138 consecutive patients younger than 18 yr of age who underwent 63,180 general anesthetics for procedures performed in all surgical specialties from July 1985 through June 1997 at the Mayo Clinic. RESULTS Pulmonary aspiration occurred in 24 patients (1: 2,632 anesthetics; 0.04%). Children undergoing emergency procedures had a greater frequency of pulmonary aspiration compared to those undergoing elective procedures (1:373 vs. 1:4,544, P < 0.001). Fifteen of the 24 children who aspirated gastric contents did not develop respiratory symptoms within 2 h of aspiration, and none of these 15 developed pulmonary sequelae. Five of these nine children who aspirated and in whom respiratory symptoms developed within 2 h subsequently had pulmonary complications treated with respiratory support (P < 0.003). Three children were treated with mechanical ventilation for more than 48 h, but no child died of sequelae of pulmonary aspiration. CONCLUSIONS In this study population, the frequency of perioperative pulmonary aspiration in children was quite low. Serious respiratory morbidity was rare, and there were no associated deaths. Infants and children with clinically apparent pulmonary aspiration in whom symptoms did not develop within 2 h did not have respiratory sequelae.

Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: A phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3)

The antiepileptic agent, gabapentin, has been demonstrated to relieve symptoms of peripheral neuropathy due to various etiologies. On the basis of these data, a multicenter, double‐blind, placebo‐controlled, crossover, randomized trial was conducted to evaluate the effect of gabapentin on symptoms of chemotherapy‐induced peripheral neuropathy (CIPN).

Attention-Deficit/Hyperactivity Disorder After Early Exposure to Procedures Requiring General Anesthesia

OBJECTIVE To study the association between exposure to procedures performed under general anesthesia before age 2 years and development of attention-deficit/hyperactivity disorder (ADHD). PATIENTS AND METHODS Study patients included all children born between January 1, 1976, and December 31, 1982, in Rochester, MN, who remained in Rochester after age 5. Cases of ADHD diagnosed before age 19 years were identified by applying stringent research criteria. Cox proportional hazards regression assessed exposure to procedures requiring general anesthesia (none, 1, 2 or more) as a predictor of ADHD using a stratified analysis with strata based on a propensity score including comorbid health conditions. RESULTS Among the 5357 children analyzed, 341 ADHD cases were identified (estimated cumulative incidence, 7.6%; 95% confidence interval [CI], 6.8%-8.4%). For children with no postnatal exposure to procedures requiring anesthesia before the age of 2 years, the cumulative incidence of ADHD at age 19 years was 7.3% (95% CI, 6.5%-8.1%). For single and 2 or more exposures, the estimates were 10.7% ( 95% CI, 6.8%-14.4%) and 17.9% ( 95% CI, 7.2%-27.4%), respectively. After adjusting for gestational age, sex, birth weight, and comorbid health conditions, exposure to multiple (hazard ratio, 1.95; 95% CI, 1.03-3.71), but not single (hazard ratio,1.18; 95% CI, 0.79-1.77), procedures requiring general anesthesia was associated with an increased risk for ADHD. CONCLUSION Children repeatedly exposed to procedures requiring general anesthesia before age 2 years are at increased risk for the later development of ADHD even after adjusting for comorbidities.

Angiotensin system inhibitors in a general surgical population.

We studied the relationship between the timing of discontinuing chronic angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor subtype 1 antagonists (ARA) and hypotension after the induction of general anesthesia in a general surgical population. We retrospectively studied 267 hypertensive patients receiving chronic ACEI/ARA therapy undergoing elective noncardiac surgery under general anesthesia. During preoperative visits, patients were asked to either take their last ACEI/ARA therapy on the morning of surgery or withhold it up to 24 h before surgery. The number of hours from the last ACEI/ARA dose to surgery was recorded during the preoperative interview. Electronic medical and anesthesia records were reviewed for comorbidities, type and dose of anesthetics used, intraoperative hemodynamics, IV fluids, perioperative vasopressor administration, and rate of severe postoperative complications. Arterial blood pressure (BP) and heart rate were recorded during the 60-min postinduction period, and hypotension was classified as moderate (systolic BP ≤85 mm Hg) and severe (systolic BP ≤65 mm Hg). We analyzed all variables separately for patients who took their last ACEI/ARA therapy <10 h and ≥10 h before surgery. During the first 30 min after anesthetic induction, moderate hypotension was more frequent in patients whose most recent ACEI/ARA therapy was taken <10 h (60%) compared with those who stopped it ≥10 h (46%) before induction (P = 0.02). The adjusted odds ratio for moderate hypotension was 1.74 (95% confidence interval, 1.03–2.93) for those who took their ACEI/ARA therapy <10 h before surgery (P = 0.04). There were no differences between groups in the incidence of severe hypotension, nor was there a difference in the use of vasopressors. During the 31–60 min after induction, the incidence of either moderate (P = 0.43) or severe (P = 0.97) hypotension was similar in the two groups. No differences in postoperative complications were found between groups. In conclusion, discontinuation of ACEI/ARA therapy at least 10 h before anesthesia was associated with a reduced risk of immediate postinduction hypotension.

Perioperative Respiratory Complications in Patients with Asthma

Background Patients with asthma are thought to be at high risk for pulmonary complications to develop during the perioperative period, and these complications may lead to serious morbidity. Existing medical records were reviewed to determine the frequency of and risk factors for perioperative pulmonary complications in a cohort of residents of Rochester, Minnesota, who had asthma and who underwent anesthesia and surgery at the Mayo Clinic in Rochester. Methods Medical records were reviewed for all residents of Rochester, Minnesota, who were initially diagnosed as having definite asthma according to strict criteria from 1 January 1964 through 31 December 1983 who subsequently had at least one surgical procedure involving a general anesthetic or central neuroaxis block at the Mayo Clinic (n = 706). Results Bronchospasm was documented in the perioperative records of 12 patients (1.7% [exact 95% confidence interval, 0.9 to 3%]). Postoperative respiratory failure developed in one of these patients. Laryngospasm developed in two additional patients during operation. All episodes of bronchospasm and laryngospasm in the immediate perioperative period were treated successfully. No episodes of pneumothorax, pneumonia, or death in the hospital were noted. For univariate analysis, characteristics associated with complications included the recent use of antiasthmatic drugs, recent asthma symptoms, and recent therapy in a medical facility for asthma. Patients in whom complications developed were significantly older at diagnosis and at surgery. Conclusions The frequency of perioperative bronchospasm and laryngospasm was surprisingly low in this cohort of persons with asthma. These complications did not lead to severe respiratory outcomes in most patients. The frequency of complications was increased in older patients and in those with active asthma.

Perioperative cardiac arrests in children between 1988 and 2005 at a tertiary referral center: A study of 92,881 patients

Background:The objective of this study was to determine the incidence and outcome of perioperative cardiac arrest (CA) in children younger than 18 yr undergoing anesthesia for noncardiac and cardiac procedures at a tertiary care center. Methods:After institutional review board approval (Mayo Clinic, Rochester, Minnesota), all patients younger than 18 yr who had perioperative CA between November 1, 1988, and June 30, 2005, were identified. Perioperative CA was defined as a need for cardiopulmonary resuscitation or death during anesthesia care. A cardiac procedure was defined as a surgical procedure involving the heart or great vessels requiring an incision. Results:A total of 92,881 anesthetics were administered during the study period, of which 4,242 (5%) were for the repair of congenital heart malformations. The incidence of perioperative CA during noncardiac procedures was 2.9 per 10,000, and the incidence during cardiac procedures was 127 per 10,000. The incidence of perioperative CA attributable to anesthesia was 0.65 per 10,000 anesthetics, representing 7.5% of the 80 perioperative CAs. Both CA incidence and mortality were highest among neonates (0–30 days of life) undergoing cardiac procedures (incidence: 435 per 10,000; mortality: 389 per 10,000). Regardless of procedure type, most patients who experienced perioperative CA (88%) had congenital heart disease. Conclusion:The majority of perioperative CAs were caused by factors not attributed to anesthesia, in distinction to some recent reports. The incidence of perioperative CA is many-fold higher in children undergoing cardiac procedures, suggesting that definition of case mix is necessary to accurately interpret epidemiologic studies of perioperative CA in children.