General anesthesia Opioids

The opioids have long been recognised to inhibit hormone release from the hypothalamus and pituitary glands. Although the adrenals were discovered to respond to exogenous injection of ACTH, morphine was found to decrease the release of corticotropin and, consequently, cortisol in normal and stress situations. Morphine's suppressant effects can be traced back to the hypothalamus. [1]

Until the beginning of cardiopulmonary bypass, the secretion of growth hormone and the release of cortisol are both suppressed by high doses of morphine used in cardiac surgery (CPB). Pituitary hormone secretion is blocked by fentanyl, sufentanil, and alfentanil until circulatory bypass is initiated [2]. The physiological changes brought on by CPB are so extensive that opioids will not be able to fully suppress the hypothalamic and pituitary responses. If the surgeon uses a high dose of opioids, the patient will need ventilator assistance after surgery.

Fentanyl is used to prevent the rise in growth hormone, cortisol, and blood sugar that occurs during pelvic surgery. [3]

Systemic opioids are less effective than local anesthetics in reducing the stress reaction following abdominal surgery. A study found that while using fentanyl totally eliminated the hormonal alterations seen following traditional cholecystectomy, the approach resulted in respiratory depression needing ventilatory support in the postoperative phase. [4]

Etomidate and benzodiazepines

By inhibiting 11-hydroxylase and cholesterol side-chain cleavage enzyme, the anesthetic induction drug etomidate disrupts steroid synthesis in the adrenal cortex. Both aldosterone and cortisol production are inhibited. The effects of a single induction dosage of the medication last for 6-12 hours, 48 and those of a 1-2-hour infusion prevent cortisol synthesis for up to 24 hours [5]. In healthy patients, a cortisol inhibitor infusion after pelvic surgery has little effect on the cardiovascular system, and it has only a mild effect on metabolism by blunting the anticipated glycemic response. [6]

The benzodiazepine, midazolam, which has an imidazole ring in addition to the basic benzodiazepine structure, attenuates the cortisol responses to both peripheral and upper abdominal surgery [7]. In vitro, both midazolam and diazepam reduce cortisol secretion by bovine adrenocortical cells.

Clonidine

As an antihypertensive medication, clonidine works by stimulating alpha-2 adrenergic receptors in the brain [8]. Its sympatholytic effect helps keep blood pressure steady, and it can lessen the need for anesthesia, pain medication, and drowsiness. The stress reactions mediated by the sympathetic nervous system are suppressed by the alpha-2 agonists, lowering sympathetic, adrenal, and cardiovascular responses to unpleasant surgical stimuli.

Regional Anesthesia

When local anesthetics are injected into the spinal column to produce complete epidural analgesia, the hormonal and metabolic responses to pelvic and lower limb surgery are avoided. It has been shown that hysterectomy-induced spikes in cortisol and glucose concentrations can be avoided with a preoperative epidural inhibition of dermatomal segments T4 to S5 [9]. The operative site's afferent input to the CNS and the hypothalamic-pituitary axis, as well as the efferent autonomic neuronal connections to the liver and adrenal medulla, are both cut off. Therefore, both the adrenocortical and the glycemic reactions to surgery are nullified. Hormonal and metabolic alterations cannot be prevented entirely by less comprehensive brain blockage.

Even with thorough epidural local anesthetic blockade, pituitary hormone reactions cannot be totally prevented in upper abdominal or thoracic surgery. Bromage and coworkers found that an epidural block up to the C6 dermatome reduced postoperative glycaemic alterations but not the elevations in cortisol concentrations [10]. There have been several proposed explanations for why the stress reactions have not been eliminated entirely in these experiments. Efferent blockade of nerves to the adrenal medulla and the liver inhibits hyperglycaemic responses, and most of these issues revolve around inadequate or incomplete afferent somatic and sympathetic neural blockade, which allows pituitary activation and, by extension, cortisol release from the adrenal cortex in response to ACTH.

Cardiac Surgery

Treatment of patients undergoing coronary artery bypass grafting has benefited from the use of perioperative thoracic epidural anesthesia [11]. Researchers have looked into how thoracic epidural analgesia affects physiological factors and neuroendocrine production. Using thoracic epidural analgesia in conjunction with general anesthesia, it is possible to prevent alterations in catecholamine responses during CPB and for up to 24 hours following the beginning of heart surgery [12]. In other words, opioid anesthesia is insufficient for this purpose. There is some evidence that thoracic epidural analgesia can reduce the cortisol responses to CPB.

The use of thoracic epidural analgesia in cardiac surgery may have several potential benefits in terms of improvements in organ function, despite the fact that there is no direct link between the attenuation of hormonal and metabolic reactions and postoperative outcome. Strong analgesia is provided via thoracic epidural anesthesia, which also helps to improve pulmonary function after surgery and decrease the need for systemic opioids [13]. Hypercoagulability, or excessive blood clotting, is common during surgery, but this could help lower that risk. [14]

Troponin T, a contractile protein unique to the heart, is a sensitive biochemical marker of myocardial damage. Myocardial ischaemia can be evaluated by measuring the protein's serum level. Recent research has linked the use of thoracic epidural anesthesia and general anesthesia for heart surgery with reduced myocardial injury, as measured by reduced troponin T release [15]. Thoracic epidural analgesia has been utilized well to treat refractory angina in medical patients. Blocking cardiac sympathetic efferents and afferents has sympatholytic effects, which may help restore a healthy oxygen supply-demand ratio. Recently, researchers have analyzed the effectiveness of thoracic epidural anesthesia for patients with heart problems. [16]

The Stress Response and Surgical Outcome

Many researchers have been interested in the effects of reducing stress on surgical outcomes. The degree to which reactions are altered is determined by the specific analgesic methods employed. Neuronal inhibition with local anesthetics is particularly effective at reducing stress reactions. Because of this, research into regional anesthetic and analgesic regimes, especially epidural blocking using local anesthetic drugs, has been extensively conducted. Providers of analgesia through neural blockage have been shown in separate research to ameliorate a variety of physiological characteristics of targeted organ systems. The incidence of major problems following surgery is generally low, and the numbers of patients analyzed are often too small for single research to reveal advantages in morbidity and death. In order to prove that localized analgesia improves surgical success, more and more researchers are turning to meta-analysis.

Beneficial Effects of Regional Analgesia

Thromboembolic complications: Regional analgesic techniques reduce the incidence of thromboembolic complications following surgery of the pelvis and lower limbs [17]. In upper abdominal procedures, there is not quite the same benefit in the incidence of thrombotic episodes.

Pulmonary Function

It is reasonable to expect that excellent analgesia using localized procedures will result in fewer postoperative pulmonary problems, but this has not been definitively proved. Continuous injection of epidural local anesthetic reduces the risk of pulmonary problems, according to a meta-analysis, but other methods, such as the use of systemic or epidural opioids, were less beneficial in single studies. [18]

Cardiac Complications

The sympathetic activation of the cardiovascular system during surgery can cause significant discomfort, however regional analgesia can significantly reduce this discomfort. It has not been determined whether neural blockade approaches have a greater positive impact on cardiac morbidity and outcome than other forms of pain treatment.

Gastrointestinal Function

Continuous epidural analgesia at the thoracic level decreases paralytic ileus following abdominal procedures. When compared to systemic or epidural opioids, local analgesia, or a combination of local and opioid analgesia, was superior in its ability to prevent ileus. Early use of enteral feeding, made possible by the resolution of ileus, is a major contributor to lowering the risk of infection complications.

Despite evidence that regional analgesia confers beneficial effects on organ function, improvements in overall postoperative morbidity and length of hospital stay have not been demonstrated conclusively. 

Recovery

Whether or not a patient can return home and start work after major surgery depends on a number of factors, not the least of which is their analgesic regimen. The method of surgery is crucial; patients who have laparoscopic procedures tend to recover quickly and be able to leave the hospital sooner. Patients' and doctors' and nurses' expectations, among other things, should not be overlooked. A patient's response to surgery may include a shift in behavior and/or mental state. Malaise and postoperative weariness significantly impact how quickly patients heal and are able to return to work after surgery. Fatigue after surgery is a multifaceted problem that can be mitigated in a number of ways, such as by opting for less invasive procedures and avoiding sleep disruptions. Such an "intense" strategy may be expensive in terms of staff time, but it may pay off in the form of a speedy recovery and home release from the hospital.

Several hormonal changes are triggered by neuronal activation of the hypothalamic-pituitary-adrenal axis as part of the stress response following surgery. The net effect on metabolism is a catabolic one, meaning that reserves of energy are broken down. The extent and length of the response are generally proportional to the severity of the surgical injury and the presence of complications like sepsis. In addition to the aforementioned, surgery also causes other alterations, most notably an uptick in cytokine production caused by a localized tissue reaction to injury. Local anesthetics used for regional anesthesia reduce the body's stress reaction during surgery, improving recovery and influencing postoperative success.Several hormonal changes are triggered by neuronal activation of the hypothalamic-pituitary-adrenal axis as part of the stress response following surgery. The net effect on metabolism is a catabolic one, meaning that reserves of energy are broken down. The extent and length of the response are generally proportional to the severity of the surgical injury and the presence of complications like sepsis. In addition to the aforementioned, surgery also causes other alterations, most notably an uptick in cytokine production caused by a localized tissue reaction to injury. Local anesthetics used for regional anesthesia reduce the body's stress reaction during surgery, improving recovery and influencing postoperative success.

Conflict of Interest

None declared

Funding

No funding sources

Ethical Approval

The study was approved by the Institutional Ethics Committee of Civil Hospital Nurpur

1. McDonald, Roger K. et al. “Effect of Morphine and Nalorphine on Plasma Hydrocortisone Levels in Man.” Journal of Pharmacology and Experimental Therapeutics, vol. 125, no. 3, 1959, pp. 241–247. https://jpet.aspetjournals.org/content/125/3/241.short.

2. Desborough, Joan P., and George M. Hall. “Modification of the Hormonal and Metabolic Response to Surgery by Narcotics and General Anaesthesia.” Baillière’s Clinical Anaesthesiology, vol. 3, no. 2, 1989, pp. 317–334. https://doi.org/10.1016/S0950-3501(89)80003-0.

3. Hall, G.M. et al. “Substrate Mobilisation during Surgery. A Comparison between Halothane and Fentanyl Anaesthesia.” Anaesthesia, vol. 33, no. 10, 1978, pp. 924–930. https://europepmc.org/article/med/727414.

4. Klingstedt, C. et al. “High- and Low-Dose Fentanyl Anaesthesia: Circulatory and Plasma Catecholamine Responses during Cholecystectomy.” British Journal of Anaesthesia, vol. 59, no. 2, 1987, pp. 184–188. https://doi.org/10.1093/bja/59.2.184.

5. Moore, R.A. et al. “Peroperative Endocrine Effects of Etomidate.” Anaesthesia, vol. 40, 1985, pp. 124–130.

6. Desborough, J.P. et al. “Midazolam Modifies Pancreatic and Anterior Pituitary Hormone Secretion during Upper Abdominal Surgery.” British Journal of Anaesthesia, vol. 67, no. 4, 1991, pp. 390–396. https://doi.org/10.1093/bja/67.4.390.

7. Aantaa, R., and M. Scheinin. “Alpha2-Adrenergic Agents in Anaesthesia.” Acta Anaesthesiologica Scandinavica, vol. 37, no. 5, 1993, pp. 433–448. https://doi.org/10.1111/j.1399-6576.1993.tb03743.x.

8. Engquist, Allan et al. “The Blocking Effect of Epidural Analgesia on the Adrenocortical and Hyperglycemic Responses to Surgery.” Acta Anaesthesiologica Scandinavica, vol. 21, no. 4, 1977, pp. 330–335. https://doi.org/10.1111/j.1399-6576.1977.tb01227.x.

9. Bromage, P.R. “Influence of Prolonged Epidural Blockade on Blood Sugar and Cortisol Response to Operations upon the Upper Part of the Abdomen and the Thorax.” Surgery, Gynecology & Obstetrics, vol. 132, 1971, pp. 1051–1056. https://cir.nii.ac.jp/crid/1570009750303020032.

10. Liem, Tiong H. et al. “Coronary Artery Bypass Grafting Using Two Different Anesthetic Techniques: Part 2: Postoperative Outcome.” Journal of Cardiothoracic and Vascular Anesthesia, vol. 6, no. 2, 1992, pp. 156–161. https://doi.org/10.1016/1053-0770(92)90190-I.

11. Moore, C.M. et al. “Hormonal Effects of Thoracic Extradural Analgesia for Cardiac Surgery.” British Journal of Anaesthesia, vol. 75, no. 4, 1995, pp. 387–393. https://doi.org/10.1093/bja/75.4.387.

12. Tuman, Kenneth J. et al. “Effects of Epidural Anesthesia and Analgesia on Coagulation and Outcome after Major Vascular Surgery.” Anesthesia & Analgesia, vol. 73, no. 6, 1991, pp. 696–704. https://journals.lww.com/anesthesia-analgesia/abstract/1991/12000/effects_of_epidural_anesthesia_and_analgesia_on.5.aspx.

13. Loick, Heinz Michael et al. “High Thoracic Epidural Anesthesia, but Not Clonidine, Attenuates the Perioperative Stress Response via Sympatholysis and Reduces the Release of Troponin T in Patients Undergoing Coronary Artery Bypass Grafting.” Anesthesia & Analgesia, vol. 88, no. 4, 1999, pp. 701–709. https://doi.org/10.1213/00000539-199904000-00001.

14. Meissner, Andreas, Norbert Rolf, and H.U.G.O. Van Aken. “Thoracic Epidural Anesthesia and the Patient with Heart Disease: Benefits, Risks, and Controversies.” Survey of Anesthesiology, vol. 42, no. 6, 1998, p. 353. https://journals.lww.com/surveyanesthesiology/citation/1998/12000/Thoracic_Epidural_Anesthesia_and_the_Patient_with.48.aspx.

15. Lyons, F.M., and K. Meeran. “The Physiology of the Endocrine System.” International Anesthesiology Clinics, vol. 35, 1997, pp. 1–21.

16. Ballantyne, Jane C. et al. “The Comparative Effects of Postoperative Analgesic Therapies on Pulmonary Outcome: Cumulative Meta-Analyses of Randomized, Controlled Trials.” Anesthesia & Analgesia, vol. 86, no. 3, 1998, pp. 598–612. https://doi.org/10.1213/00000539-199803000-00032.

17. Kehlet, Henrik. “Acute Pain Control and Accelerated Postoperative Surgical Recovery.” Surgical Clinics of North America, vol. 79, no. 2, 1999, pp. 431–443. https://doi.org/10.1016/S0039-6109(05)70390-X.

18. Steinbrook, Richard A. “Epidural Anesthesia and Gastrointestinal Motility.” Anesthesia & Analgesia, vol. 86, no. 4, 1998, pp. 837–844. https://doi.org/10.1213/00000539-199804000-00029.