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Sufentanil is a new synthetic opioid 5–10 times as potent as fentanyl. This study evaluated the endocrine and metabolic responses to cardiac surgery in 10 patients anesthetized with 20 μ/kg of sufentanil and air-O2. With the exception of prolactin, there were no significant changes in the concentrations of any of the hormones or substrates measured before cardiopulmonary bypass. No changes occurred at any time during the study in insulin or growth hormone concentrations and only plasma cortisol increased significantly 1 h after surgery. Blood glucose increased significantly at the end of cardiopulmonary bypass and remained elevated throughout the remainder of the study period. ADH also increased during bypass, although the increase only reached significance (P < 0.05) at the end of surgery. Marked increases in concentrations of nonesterified fatty acids and decreases in levels of triglycerides occurred immediately before and during bypass. These changes are attributed to the effect of heparin on lipoprotein lipase activity. Highly significant (P < 0.01) increases occurred in plasma lactate concentrations during cardiopulmonary bypass. This is attributed to use of Ringer's lactate solution in the oxygenator prime. Very large increases in catecholamine concentrations occurred during cardiopulmonary bypass. Thus, although sufentanil prevents the endocrine and metabolic responses to surgery before cardiopulmonary bypass, even the use of a large dose is ineffective in preventing these responses during or after bypass.