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K J Anand

Publications and source records attributed to K J Anand.

18 recordsLinked to original sources

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

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.

Acetoacetates

Neonatal pain management.

Neonatal pain management is a challenge for the clinician. Research is just beginning to uncover the neonates' capability of expression of pain, explore pharmacologic management strategies, and identify the spectrum of intrusions that may precipitate pain or distress in the critically ill neonate. This article reviews the neonatal biologic, behavioral, and physiologic responses to pain and describes recommendations for clinical management and decision-making.

Critical Care

Hormonal-metabolic stress responses in neonates undergoing cardiac surgery.

Hormonal and metabolic responses were measured in 15 neonates who underwent repair of complex congenital heart defects during a standardized anesthetic protocol. Four of the 15 neonates died postoperatively in the intensive care unit. Analysis of arterial plasma samples obtained before, during, and 24 h after surgery showed that plasma epinephrine, norepinephrine, cortisol, glucagon, and beta endorphin increased in all patients (P less than 0.05). Insulin levels increased only at the end of surgery but remained elevated for 24 h postoperatively (P less than 0.02). Intraoperative metabolic changes were characterized by hyperglycemia and lactic acidemia that persisted postoperatively. This pattern of neonatal stress responses is distinct from and more extreme than that seen in adult cardiac surgical patients. The four neonates who died postoperatively tended to have higher stress responses intra- and postoperatively despite having been indistinguishable from survivors by the usual clinical and hemodynamic criteria. These preliminary results suggest that neonatal hormonal and metabolic responses to cardiac surgical operations in neonates are extreme and are associated with a high hospital mortality rate.

Alanine

Neonatal stress responses to anesthesia and surgery.

Neonatal stress responses have been investigated only in recent years. Term neonates mount substantial hormonal and metabolic responses, which are distinct from those of adult patients. These responses can be altered significantly by the effects of prematurity, the effects of graded surgical stress, and the anesthetic techniques used during surgery. In addition, neonatal stress responses may have important implications for the clinical outcome following surgery in neonates.

Anesthesia

The neuroanatomy, neurophysiology, and neurochemistry of pain, stress, and analgesia in newborns and children.

Beginning with a brief description of mature anatomic pathways and neurotransmitters in the "pain system," this article details their development in the human fetus, neonate, and child. Special emphasis is given to the basic mechanisms and physiologic effects of opioid analgesia. The clinical implications of these data are described, particularly with regard to the maintenance of cardiovascular stability and hormonal-metabolic homeostasis in newborns and children undergoing surgery or other forms of stress.

Analgesics

Management of pain in the postoperative neonate.

Only recently has the use of anesthesia and analgesia become widely accepted in the newborn infant. This is largely a result of the overwhelming evidence that neonates have the neurologic substrate for the perception of pain and display characteristic behavioral, physiologic, metabolic, and hormonal responses to noxious stimuli. The management of postoperative pain in the surgical neonate begins in the operating room, where techniques can be chosen that will ease the transition into the postoperative period. For postoperative analgesia, the most widely used and effective agents are the narcotics morphine and fentanyl. They may be administered either intermittently or continuously, and with proper precautions may be given to both intubated and nonintubated newborns. Other medications for analgesia and sedation are not as well studied in the newborn, but chloral hydrate and the benzodiazepines are useful for sedation, and acetaminophen may be used for analgesia alone or for potentiating the effect of narcotics. In addition, a number of creative nonpharmacologic techniques are being developed and promise to further decrease the discomfort experienced by postoperative neonates.

Analgesia

Does halothane anaesthesia decrease the metabolic and endocrine stress responses of newborn infants undergoing operation?

Concern about the side effects of various anaesthetic agents in newborn infants has led to the widespread use of anaesthesia with unsupplemented nitrous oxide and oxygen with muscle relaxants in such patients. To investigate the efficacy of such a regimen 36 neonates undergoing operations were randomised to two groups: one group received anaesthesia with nitrous oxide and curare alone and the other was additionally given halothane. Concentrations of metabolites and hormones were measured before and at the end of operation and at six, 12, and 24 hours after operation and the values compared between the two groups. Neonates given halothane anaesthesia showed decreased hormonal responses to operation, with significant differences between the two groups in the changes in adrenaline, noradrenaline, and cortisol concentrations and the ratio of insulin to glucagon concentration. Changes in blood concentrations of glucose and total ketone bodies and plasma concentrations of non-esterified fatty acids were also decreased in neonates receiving halothane anaesthesia. Neonates given anaesthesia with unsupplemented nitrous oxide showed significantly greater increases in the urinary ratio of 3-methylhistidine to creatinine concentration and their clinical condition was also more unstable during and after operation. Unless specifically contraindicated potent anaesthesia with halothane or other anaesthetic agents should be given to all neonates undergoing surgical operations as it decreases their stress responses and improves their clinical stability during and after operation.

Adrenal Cortex Hormones

Measuring the severity of surgical stress in newborn infants.

Measurement of the severity of surgery would greatly facilitate the design and interpretation of studies in neonates undergoing surgery. A scoring method, based on the amount of blood loss, superficial dissection, and visceral trauma, the site and duration of surgery, cardiac surgical factors, and associated stress factors for surgical neonates, was formulated and applied to 94 neonates undergoing surgery. Perioperative management was standardized for all patients and hormonal-metabolic variables were measured in blood samples drawn preoperatively at the end of the operation, and at six, 12, and 24 hours after operation. The stress scores were correlated significantly with the plasma epinephrine (P less than .0001), norepinephrine (P less than .0001), insulin (P less than .001), glucagon (P less than .005), and cortisol (P less than .02) responses, and with changes in blood glucose (P less than .0001), lactate (P less than .0001), pyruvate (P less than .0001), and alanine (P less than .005) during and after operation. Discriminant function analysis was used for further validation and this scoring method was found to predict accurately the severity of surgical stress in 89.4% cases. Discrepancies in the remaining cases were found to be related to specific clinical factors. On comparison of the hormonal and metabolic responses of neonates in the minor (N = 71), moderate (N = 12), and severe (N = 11) stress groups, increasing severity of surgical stress was found to be associated with greater and more prolonged changes in plasma catecholamines, blood glucose, and gluconeogenic substrates during and after operation. Clinical outcome following operation was also significantly different between the three stress groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine

Antenatal fetal heart rate variation in relation to the respiratory and metabolic status of the compromised human fetus.

Three groups of women were delivered by caesarean section before labour: for an abnormal fetal heart rate (FHR) trace (21 cases, group 1), or for maternal deterioration in severe pre-eclampsia without gross fetal heart rate abnormalities (20 cases, group 2), or to avoid mechanical difficulties in labour at term (30 cases, group 3). The mean gestational ages of the first two groups were 32 weeks with a high proportion of infants small-for-gestational-age. In group 1, FHR variation (mean range of pulse intervals) was less than half (20.6 SE 1.2 ms) of the normal value at the same age (44.4 SE 1.5 ms). This was associated with hypoxaemia (mean umbilical artery PO2 of 6 mmHg at delivery), with evidence of compensation shown by an elevated amniotic fluid erythropoietin. The fetuses were hypoglycaemic and had greater umbilical artery blood alanine concentrations, but no large changes in adenine nucleotide or endorphin plasma concentrations. Although there was a minor degree of respiratory acidaemia at birth, there was not significant metabolic acidaemia. The results demonstrate that the reduced variation of 'suboptimal' and 'decelerative' fetal heart rate records is associated with fetal hypoxaemia and evidence of nutritional deprivation, but not with asphyxia.

Cesarean Section

Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response.

In a randomised controlled trial, preterm babies undergoing ligation of a patent ductus arteriosus were given nitrous oxide and d-tubocurarine, with (n = 8) or without (n = 8) the addition of fentanyl (10 micrograms/kg intravenously) to the anaesthetic regimen. Major hormonal responses to surgery, as indicated by changes in plasma adrenaline, noradrenaline, glucagon, aldosterone, corticosterone, 11-deoxycorticosterone, and 11-deoxycortisol levels, in the insulin/glucagon, molar ratio, and in blood glucose, lactate, and pyruvate concentrations were significantly greater in the non-fentanyl than in the fentanyl group. The urinary 3-methylhistidine/creatinine ratios were significantly greater in the non-fentanyl group on the second and third postoperative days. Compared with the fentanyl group, the non-fentanyl group had circulatory and metabolic complications postoperatively. The findings indicate that preterm babies mount a substantial stress response to surgery under anaesthesia with nitrous oxide and curare and that prevention of this response by fentanyl anaesthesia may be associated with an improved postoperative outcome.

Anesthesia, General

The stress response to surgical trauma: from physiological basis to therapeutic implications.

The response to surgical injury is mediated through the hypothalamus and is characterised by the release of catecholamines, glucocorticoids, growth hormone and glucagon; the suppression of insulin secretion and changes in other endocrine systems. These hormonal responses trigger a cascade of metabolic adjustments leading to catabolism and substrate mobilization in the postoperative period. There is evidence that a severe and prolonged catabolic reaction to injury may be associated with an increased morbidity and mortality in high-risk adult patients. This article reviews the historical background of investigation in this field, together with recent advances in the understanding of the complex metabolic phenomena following surgery. These changes are discussed with particular reference to therapeutic manipulation of the stress response using anaesthetic, hormonal or nutrition regimens. It is concluded that further research in this field may provide major clinical benefits in the management of critically ill patients undergoing surgical stress.

Anesthesia

Can the human neonate mount an endocrine and metabolic response to surgery?

Little is known of the ability of the human newborn infant to mount an endocrine and metabolic response to surgical trauma. Blood concentrations of glucose, lactate, pyruvate, alanine, hydroxybutyrate, acetoacetate, and glycerol together with plasma concentrations of insulin, glucagon, adrenaline, and nonadrenaline were measured in 33 infants (26 term, 7 preterm) subjected to surgery during the neonatal period. The results show that newborn infants can indeed mount a substantial endocrine and metabolic stress response, the main features of which are hyperglycemia and hyperlactatemia associated with the release of catecholamines and the inhibition of insulin secretion. There are specific differences between preterm and term neonates and between neonates anesthetised by different anesthetic techniques in the pattern of this response.

Anesthetics

Studies on the hormonal regulation of fuel metabolism in the human newborn infant undergoing anaesthesia and surgery.

Little is known of the endocrine and metabolic milieu in preterm and term neonates exposed to surgical stress. In order to define the effects of anaesthesia and surgery on the hormonal regulation of intermediary metabolism, the levels of plasma insulin, glucagon, adrenaline and noradrenaline were measured in addition to blood glucose, lactate, pyruvate, alanine, acetoacetate, hydroxybutyrate, glycerol and plasma-free fatty acids in 38 neonates (23 term, 15 preterm) undergoing surgery. Blood samples were drawn pre-operatively, at the end of surgery, and at 6, 12 and 24 h post-operatively. Plasma levels of adrenaline and noradrenaline increased significantly in response to surgery. In term neonates, plasma insulin concentrations were unaltered at the end of surgery, but were significantly increased throughout the post-operative period; plasma glucagon levels were unchanged at the end of surgery but had significantly decreased by 24 h after surgery. Insulin levels in preterm neonates remained unchanged during surgery as well as in the post-operative period. All neonates developed a significant peri-operative hyperglycaemia which persisted up to 12 h after surgery. Blood lactate and pyruvate increased during surgery, accompanied by significant increases in plasma free fatty acids, total ketone bodies and glycerol concentrations by the end of surgery. Blood glucose concentrations were significantly correlated with plasma adrenaline levels at the end of surgery and with plasma glucagon at 6 h post-operatively. The insulin/glucose ratio was significantly decreased at the end of surgery in term and preterm neonates. Further analysis showed that total parenteral nutrition given just before surgery and thiopentone anaesthesia given during surgery significantly augmented the peri-operative hyperglycaemic response of term neonates. Thus, stress-related hormonal changes in preterm and term neonates may precipitate a catabolic state characterized by glycogenolysis, gluconeogenesis, lipolysis and mobilization of gluconeogenic substrates in the post-operative period. Prevention of these metabolic derangements by anaesthetic or hormonal manipulation may possibly help to improve the clinical outcome of neonates undergoing surgery.

Anesthesia, General