The effects of anesthesia and surgery can lead to stress responses that result in hormonal and metabolic changes in the body. The immune system and the nervous system communicate both ways, and it was found that nociception and proinflammatory cytokines play a joint regulatory role, i.e., increased production of proinflammatory cytokines can worsen the pain. Major surgery can trigger the release of cytokines such as IL-1, IL-6, and TNF-α.

The effects of anesthesia and surgery can lead to stress responses that result in hormonal and metabolic changes in the body. The immune system and the nervous system communicate both ways, and it was found that nociception and proinflammatory cytokines play a joint regulatory role, i.e., increased production of proinflammatory cytokines can worsen the pain. Major surgery can trigger the release of cytokines such as IL-1, IL-6, and TNF-α.

The acute analgesic effect of ketamine is generally believed to be mediated through the blockade of the phencyclidine binding site of the N-methyl-d-aspartate (NMDA) receptor of nociceptive neurons. Ketamine can reduce the inflammatory response marked by a decrease in CRP levels to surgical trauma and can prevent secondary damage to tissues/organs that were not initially affected by surgery by reducing inflammation. This also reduces postoperative pain and analgesics.

Inclusion Criteria:

1. Patients undergoing elective laparotomy with general anesthesia at Sanglah Hospital from July to September 2020.
2. Patients aged 18-65 years.
3. Patient physical status American American Society of Anesthesiologist (ASA) 1 and 2.

Exclusion Criteria:

1. Contraindication to ketamine.
2. Allergy to morphine
3. Presence of cardiorespiratory chronic diseases.
4. Presence of autoimmune diseases.
5. History of the central nervous system or psychiatric disorders.
6. BMI <18.5 kg/m2 or ≥30 kg/m2.
7. A history of chronic pain killer medications (such as opioid or non-steroidal anti- inflammatory drugs)

Drop Out Criteria

1. Patients with class 3 bleeding during the surgery
2. Patients with more than 5-hours duration of surgery
3. Patients need mechanical ventilation after the surgery

Only care providers involved directly with the subjects in the operating room are not masked.