Newborn anaesthesia: pharmacological considerations.

Inhalation anaesthetics For the inhalation anaesthetics there are age-related differences in uptake and distribution, in anaesthetic requirements as reflected by differences in MAC, in the effects on the four determinants of cardiac output (preload, afterload, heart rate and contractility), and in the sensitivity of protective cardiovascular reflexes (e.g., baroreceptor reflex). These differences limit the margin of safety of the potent agents in infants. Alveolar uptake of inhalation anaesthetics and hence whole-body uptake is more rapid in infants than in adults. J Lung washout is more rapid in infants than in adults because of the larger ratio between alveolar minute ventilation and lung volume (FRC) (3.5:1 in the infant vs. 1.3:1 in the adult). Increased brain size (ml.kg-J), limited muscle mass, limited fat content, and proportional differences in the distribution of cardiac output contribute to differences in uptake. Age-related differences in tissue partition coefficients also influence the equilibrium tissue concentration and the rate of change in the tissue concentration. Early in an anaesthetic induction (at equal inspired concentrations) the infant will have higher tissue concentrations in brain, heart, and muscle than will the adult. MAC, an estimate of anaesthetic requirement, is, in part, age related. 2 Neonates require 25 per cent less anaesthetic than infants; infants have a greater anesthetic requirement than older patients. MAC is dramatically lower in newly born animals than in their 12-hour-old counterparts. The response of the newborn to painful stimuli is attenuated even in the awake state. Most likely this is related to the immaturity of the central nervous system; elevated concentrations of progesterone and 13-endorphin and 13-1ipoproteins may also play a role in the decrease in MAC in neonates. Several investigators have studied the age-related cardiovascular effects of the potent inhalation anaesthetics at known multiples of MAC. At end-tidal concentrations of halothane bracketing MAC, Lerman er al . 2 noted no difference in the incidence of hypotension or bradycardia in neonates and in infants one to six months of age. Likewise, we 3 have noted no age-related differences in the determinants of cardiac output in developing piglets 1-20 days during either halothane or isoflurane anaesthesia. Halothane produced hypotension by a reduction in contractility and heart rate; in much older animals halothane also decreases peripheral vascular resistance. In piglets although blood pressure was equally depressed with isoflurane and halothane, cardiac output was better preserved during isoflurane anaesthesia. In awake man or animals decreases in blood pressure are compensated for by an increase in heart rate, myocardial contractility, and peripheral vascular resistance. Potent inhalation anaesthetics depress baroreceptor reactivity in a concentration dependent manner. In infants or newborn animals baroreceptor reflexes are more depressed (at equipotent anaesthetic concentrations) than in older animals. 4'5 This further limits the safety of potent anaesthetics in infants. Moreover, Cook et a l . 6 have demonstrated that the cardiovascular index for halothane is smaller in younger animals than in older animals. The cardiovascular index is a reflection of the therapeutic index (i.e., the ratio between the anaesthetic concentration at cardiovascular collapse to that of anaesthesia). Thus, potent inhalation anaesthetics must be used with caution in newborns and infants. Because of