Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery

N Engl J Med. 1992 Jan 2;326(1):1-9. doi: 10.1056/NEJM199201023260101.


Background: Extreme hormonal and metabolic responses to stress are associated with increased morbidity and mortality in sick adults. We hypothesized that administering deep opioid anesthesia to critically ill neonates undergoing cardiac surgery would blunt their responses to stress and might improve clinical outcomes.

Methods: In a randomized trial, 30 neonates were assigned to receive deep intraoperative anesthesia with high doses of sufentanil and postoperative infusions of opiates for 24 hours; 15 neonates were assigned to receive lighter anesthesia with halothane and morphine followed postoperatively by intermittent morphine and diazepam. Hormonal and metabolic responses to surgery were evaluated by assay of arterial blood samples obtained before, during, and after the operations.

Results: The neonates who received deep anesthesia (with sufentanil) had significantly reduced responses of beta-endorphin, norepinephrine, epinephrine, glucagon, aldosterone, cortisol, and other steroid hormones; their insulin responses and ratios of insulin to glucagon were greater during the operation. The neonates who received lighter anesthesia (with halothane plus morphine) had more severe hyperglycemia and lactic acidemia during surgery and higher lactate and acetoacetate concentrations postoperatively (P less than 0.025). The group that received deep anesthesia had a decreased incidence of sepsis (P = 0.03), metabolic acidosis (P less than 0.01), and disseminated intravascular coagulation (P = 0.03) and fewer postoperative deaths (none of 30 given sufentanil vs. 4 of 15 given halothane plus morphine, (P less than 0.01).

Conclusions: In neonates undergoing cardiac surgery, the physiologic responses to stress are attenuated by deep anesthesia and postoperative analgesia with high doses of opioids. Deep anesthesia continued postoperatively may reduce the vulnerability of these neonates to complications and may reduce mortality.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetoacetates / blood
  • Analgesia / methods
  • Analgesics / administration & dosage*
  • Anesthesia, General / methods
  • Anesthetics / administration & dosage*
  • Blood Glucose / analysis
  • Cardiac Surgical Procedures*
  • Diazepam / administration & dosage
  • Epinephrine / blood
  • Female
  • Fentanyl / administration & dosage
  • Fentanyl / analogs & derivatives*
  • Halothane / administration & dosage*
  • Humans
  • Infant, Newborn
  • Insulin / blood
  • Lactates / blood
  • Lactic Acid
  • Male
  • Morphine / administration & dosage*
  • Norepinephrine / blood
  • Postoperative Care / methods
  • Stress, Physiological / prevention & control
  • Sufentanil
  • beta-Endorphin / blood


  • Acetoacetates
  • Analgesics
  • Anesthetics
  • Blood Glucose
  • Insulin
  • Lactates
  • Lactic Acid
  • beta-Endorphin
  • Morphine
  • Sufentanil
  • Diazepam
  • Fentanyl
  • Halothane
  • Norepinephrine
  • Epinephrine