ABSTRACT
BACKGROUND: Several experimental studies have suggested that early exposure to anesthetic agents, i.e., before completion of synaptogenesis, can result in widespread apoptotic neuronal degeneration and late cognitive impairment, but human data are lacking. The authors performed a retrospective pilot study to test the feasibility and calculate sample sizes for a larger epidemiologic study of disturbed neurobehavioral development as a function of age at the time of first anesthetic exposure. Pediatric urological procedures were selected because the timing of surgery depends mainly on the age at which a diagnosis is made. METHODS: Neurobehavioral development was assessed using the validated 120-item parental Child Behavior CheckList/4-18 in 314 children who were operated for pediatric urological procedures between the ages of 0 and 6 yr. RESULTS: Of 243 questionnaires returned, the total problem score was clinically deviant in 41 (23%) of children aged less than 24 months at the time of first surgery and 13 (20%) aged greater than 24 months. Crude and adjusted odds ratios for a clinically deviant Child Behavior CheckList/4-18 score increased with younger age at the time of surgery, but the confidence intervals were very wide. Adjusted odds ratio was 1.38 (0.59-3.22) when operated at age less than 6 months, 1.19 (0.45-3.18) when operated between 6 and 12 months of age, and 1.20 (0.45-3.20) when operated between 12 and 24 months (using operated at greater than 24 months of age as reference category). A properly powered cohort study would require at least 2,268 children. CONCLUSIONS: Children undergoing urologic surgery at age less than 24 months showed more behavioral disturbances than children in whom surgery was performed after age 2 yr, although the results were not statistically significant. To confirm or refute an effect of anesthesia on cognitive development, at least 2,268 children need to be studied. With retrospective study designs, residual confounding remains an issue that can only be solved in prospective randomized studies.
Subject(s)
Anesthesia, General/adverse effects , Anesthetics, General/adverse effects , Child Behavior Disorders/chemically induced , Urologic Surgical Procedures , Adolescent , Age Factors , Child , Child Behavior Disorders/diagnosis , Child Behavior Disorders/epidemiology , Feasibility Studies , Female , Humans , Male , Odds Ratio , Pilot Projects , Retrospective Studies , Sample Size , Surveys and Questionnaires , Treatment OutcomeABSTRACT
BACKGROUND: The effects of hyperthermia on the human brain are incompletely understood. This study assessed the effects of whole body hyperthermia on cerebral oxygen extraction and autoregulation in humans. METHODS: Nineteen patients with chronic hepatitis C virus infection, not responding to interferon treatment, were subjected to experimental therapy with extracorporeal whole body hyperthermia at 41.8 degrees C for 120 min under propofol anesthesia (23 sessions total). During treatment series A (13 sessions), end-tidal carbon dioxide was allowed to increase during heating. During series B (10 sessions), end-tidal carbon dioxide was maintained approximately constant. Cerebral oxygen extraction (arterial to jugular venous difference of oxygen content) and middle cerebral artery blood flow velocity were continuously measured. Cerebral pressure-flow autoregulation was assessed by static tests using phenylephrine infusion and by assessing the transient hyperemic response to carotid compression and release. RESULTS: For treatment series A, cerebral oxygen extraction decreased 2.2-fold and cerebral blood flow velocity increased 2.0-fold during heating. For series B, oxygen extraction decreased 1.6-fold and flow velocity increased 1.5-fold. Jugular venous oxygen saturation and lactate measurements did not indicate cerebral ischemia at any temperature. Static autoregulation test results indicated loss of cerebrovascular reactivity during hyperthermia for both series A and series B. The transient hyperemic response ratio did not decrease until the temperature reached approximately 40 degrees C. Per degree Celsius temperature increase, the transient hyperemic response ratio decreased 0.07 (95% confidence interval, 0.05-0.09; P = 0.000). This association remained after adjustment for variations in arterial partial pressure of carbon dioxide, mean arterial pressure, and propofol blood concentration. CONCLUSION: Profound hyperthermia during propofol anesthesia is associated with decreased cerebral oxygen extraction, increased cerebral blood flow velocity, and impaired pressure-flow autoregulation, indicating transient partial vasoparalysis.
