Comparison of Two Drugs ,i.e., Nalbuphine Vs Ketamine at Low Doses for the Peri-Operative Shivering Control in Patients Undergoing Gynaecological Surgery Under Spinal Anaesthesia

Comparison of Nalbuphin vs Ketamine for the Control of Peri-operative Shivering in Patients Undergoing Gynaecological Surgery Under Spinal Anaesthesia

Shivering is recognized as an undesirable effect of spinal anesthesia. Patients undergoing gynecological surgeries may experience increased physiological stress due to perioperative shivering. This condition can lead to serious complications such as increased oxygen consumption, resulting in hypoxemia, lactic acidosis, and elevated carbon dioxide production. Additionally, shivering may cause increased intraocular and intracerebral pressure and can interfere with monitoring techniques like pulse oximetry, blood pressure, and electrocardiography. If not treated, shivering can negatively impact patient outcomes, prolong recovery times, and extend hospital stays. The use of opioids has shown effectiveness in treating shivering. Based on the existing literature, it is hypothesized that there is no difference in the efficacy of nalbuphine and ketamine in controlling perioperative shivering in patients undergoing gynecological surgery under spinal anesthesia. Therefore, the study aims to investigate and compare the effectiveness of nalbuphine and ketamine in managing post-spinal shivering in these patients, focusing on i) incidence of shivering, ii) severity of shivering in both groups, iii) complications such as vomiting and sedation, and iv) the need for rescue medication. Preventing and managing shivering is crucial for successful surgical outcomes. To date, no comparative study has evaluated the intravenous efficacy of these two drugs in this patient population for post-spinal shivering control. This will be a double-blind, randomized controlled trial conducted in the Anesthesiology Department at DHQ Teaching Hospital Sargodha. A total of 90 gynecological patients will be enrolled and divided equally into two groups: Group N receiving nalbuphine and Group K receiving ketamine. Parameters such as heart rate, systolic and diastolic blood pressure, temperature, oxygen saturation, incidence and grade of shivering, complications like sedation and vomiting, and the need for rescue medication will be recorded. The study may face limitations due to the lack of advanced monitoring equipment for assessing parameters like core body temperature at the study site. Evaluations of cognitive and psychomotor functions cannot be conducted due to resource constraints. The use of a non-probability convenience sampling method, while practical, may introduce bias. Additionally, precise blinding may not be achievable due to limited technical personnel, and financial constraints prevent increasing the sample size.

Study Overview

• Status: Completed
• Conditions: Peri-operative Shivering Under Spinal Anaesthesia
• Intervention / Treatment: Drug: Participants assigned to this arm received injection nalbuphine.; Drug: Participants assigned to this arm received injection ketamine.

Detailed Description

Shivering, a repetitive involuntary muscular activity, is the most common problem during and after spinal anesthesia. The spinal anesthesia not only causes vasodilation, resulting in rapid loss of heat, but it also causes redistribution of heat in the peripheral areas, resulting in hypothermia and, eventually, shivering. Although it does not result in death, complications can arise in patients with a history of cardiorespiratory diseases, endangering the patients' safety. These complications include hypoxemia with increased lactic acidosis and carbon dioxide, increased oxygen consumption, increased intraocular and intracerebral pressure resulting in aggravation of post-operative pain and increased surgical bleeding that interferes with pulse rate and ECG monitoring.

Various treatments are currently available to control shivering in patients following spinal anesthesia. These include both pharmacological and non-pharmacological methods. Non-pharmaceutical methods are effective but expensive. A variety of pharmacological methods for controlling post-spinal anesthesia shivering have been suggested, including ketamine and nalbuphine as well as many others that are inexpensive and easy to use. Ketamine, a competitive receptor antagonist of N-methyl D-aspartate (NMDA), is known to reduce regional anesthesia by 70% and postoperative shivering by impairing thermoregulatory controls. It causes vasoconstriction in patients at risk of hypothermia. Ketamine controls shivering through non-shivering thermogenesis, either through the β-adrenergic effect of norepinephrine or through the hypothalamus. Nalbuphine, a semi-synthetic "class B" opioid analgesic, has both K-agonist and µ-antagonist properties. It has a high affinity for K-opioid receptors in the central nervous system. In the hypothalamus, the temperature regulation threshold is lowered by it for vasoconstriction during shivering due to the presence of high-density a2 adeno-receptors. The anti-shivering effects of intravenous ketamine and nalbuphine are poorly understood. Therefore, a double-blind, placebo-controlled, randomized study has been designed to compare the potency and efficacy of ketamine with nalbuphine and investigate the possible control mechanisms in patients undergoing gynecological surgery receiving spinal anesthesia.

The objectives of this study are to investigate and compare the effects of nalbuphine and ketamine in patients undergoing spinal anesthesia for gynecological surgeries in terms of:

1. Incidence of shivering in both study groups
2. Determine the grades of shivering
3. Complications of study drugs such as vomiting and sedation
4. Need of Rescue drug (injection of Tramadol IV 0.5 mg/kg)

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Sargodha, Pakistan
    • DHQ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

i. Female patients of age between 18 and 40 years undergoing gynecological surgeries (total abdominal hysterectomy, ovarian cystectomy, vaginal hysterectomy, myomectomy).

ii. ASA 1 and 2.

Exclusion Criteria:

i. ASA 3 and onwards as per the classification of the American Society of Anesthesiologists.

ii. Obstetric patients

iii. Patients who are allergic to study drugs.

iv. Patients undergoing general anesthesia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants assigned to this arm received injection nalbuphine.; After spinal anesthesia in a sitting position at L3-L4 or L4-L5 using a 25-gauge Quincke spinal needle, 1.2 mL of 0.75% (7.5 mg) hyperbaric bupivacaine was injected in the subarachnoid space. The Bromage scale and cold test by using a spirit swab will be used to evaluate the subarachnoid block for the desired motor and sensory blocks, respectively. After spinal anesthesia, the study drug Nalbuphin (0.07 mg/kg) will be administered intravenously to group N, and oxygen will be given through a face mask at 4 liters per minute.	Drug: Participants assigned to this arm received injection nalbuphine.; After spinal anesthesia in a sitting position at L3-L4 or L4-L5 using a 25-gauge Quincke spinal needle, 1.2 mL of 0.75% (7.5 mg) hyperbaric bupivacaine was injected in the subarachnoid space. The Bromage scale and cold test by using a spirit swab will be used to evaluate the subarachnoid block for the desired motor and sensory blocks, respectively. After spinal anesthesia, the study drug Nalbuphin (0.07 mg/kg) will be administered intravenously to group N, and oxygen will be given through a face mask at 4 liters per minute.; Other Names: Group N
Experimental: Participants assigned to this arm received injection Ketamine.; After spinal anesthesia in a sitting position at L3-L4 or L4-L5 using a 25-gauge Quincke spinal needle, 1.2 mL of 0.75% (7.5 mg) hyperbaric bupivacaine was injected into the subarachnoid space. The Bromage scale and cold test by using a spirit swab will be used to evaluate the subarachnoid block for the desired motor and sensory blocks, respectively. After spinal anesthesia, the study drug ketamine (0.2 mg/kg) will be administered intravenously to group N, and oxygen will be given through a face mask at 4 liters per minute.	Drug: Participants assigned to this arm received injection ketamine.; After spinal anesthesia in a sitting position at L3-L4 or L4-L5 using a 25-gauge Quincke spinal needle, 1.2 mL of 0.75% (7.5 mg) hyperbaric bupivacaine was injected into the subarachnoid space. The Bromage scale and cold test by using a spirit swab will be used to evaluate the subarachnoid block for the desired motor and sensory blocks, respectively. After spinal anesthesia, the study drug ketamine (0.2 mg/kg) will be administered intravenously to group N, and oxygen will be given through a face mask at 4 liters per minute.; Other Names: Group K

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of shivering in both study groups	Shivering will be assessed by the presence or absence of shivering.	Within one hour post-spinal anesthesia.
Grades of shivering	Shivering will be assessed by Tsai and Chu, with the grade of shivering as follows: Grade of shivering: clinical sign 0 No shivering; Piloerection or peripheral vasoconstriction, but no visible shivering; Muscular activity in only one muscle group; Muscular activity in more than one muscle group, but not generalized; Shivering involving the whole body	After spinal anesthesia, grades of shivering were assessed at 5 minutes and then after every 10 minutes until 60 minutes.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Heart rate will be monitored by a pulse oximeter probe.	After spinal anesthesia, heart rate will be assessed at 5 minutes and then after every 10 minutes until 60 minutes.
Oxygen Saturation	Oxygen saturation will be monitored with a pulse oximeter probe.	After spinal anesthesia, oxygen saturation was assessed at 5 minutes and then after every 10 minutes until 60 minutes.
Systolic blood pressure	Systolic blood pressure was measured with non-invasive blood pressure cuff.	After spinal anesthesia, systolic blood pressure was assessed at 5 minutes and then after every 10 minutes until 60 minutes.
Diastolic blood pressure	Diastolic blood pressure was assessed by non-invasive blood pressure cuff.	After spinal anesthesia, diastolic blood was assessed at 5 minutes and then after every 10 minutes until 60 minutes.
Temperature	Temperature was assessed by forehead temperature probe.	After spinal anesthesia, temperature was assessed at 5 minutes and then after every 10 minutes until 60 minutes.
Sedation	Sedation will be assessed by Ramsay sedation score as follows: Sedation score Sedation level; Patient is anxious and agitated or restless, or both; Patient is cooperative, oriented and tranquil; Patient responds to command only; Patient exhibits brisk response to light glabellar tap or loud auditory stimulus; Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus; Patient exhibits no response	Sedation was assessed for 1 hour post spinal anaesthesia.
Vomiting	Vomiting will be assessed clinically.	Vomiting was assessed for one hour post spinal anesthesia.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need of Rescue drug	If the grade of shivering is ≥3, then 0.5 mg/kg of injection tramadol will be administered intravenously as a second rescue plan to control shivering in both study groups.	Within one hour post-spinal anesthesia.

Collaborators and Investigators

• Sponsor: Sargodha Medical College

Publications and helpful links

Helpful Links

• Related Information

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Actual): January 1, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: April 9, 2026
• First Submitted That Met QC Criteria: April 18, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 18, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Peri-operative shivering
• Other Study ID Numbers: SMC-ANS-2025-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Your study is a single-center anesthesia comparison trial.

There is no requirement to share individual participant data (IPD).

Unless you have a formal data-sharing mechanism (repository, request process, timelines), selecting Yes will create extra mandatory fields.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No