Pre-operative Ketorolac Administration Has no Pre-emptive Analgesic Effect Following Total Abdominal Hysterectomy

Pain Clinical Trial

Official title:

Pre-operative Ketorolac Administration Has no Pre-emptive Analgesic Effect Following Total Abdominal Hysterectomy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02642718
• Other study ID #: KP 359352
• Status: Completed
• Phase: Phase 4
• First received: December 19, 2015
• Last updated: January 1, 2016
• Start date: April 2001
• Est. completion date: November 2001

Study information

• Verified date: January 2016
• Source: Hospital Arquitecto Marcide
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

Background: Experimental models using short duration noxious stimuli have led to the concept of pre-emptive analgesia. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), has been shown to have a post-operative narcotic sparing effect when given pre-operatively and alternatively to not have this effect. This study was undertaken to determine whether a single intravenous dose of ketorolac would result in decreased post-operative pain and narcotic requirements.

Methods: In a double-blind, randomized controlled trial, 48 women undergoing abdominal hysterectomy were studied. Patients in the ketorolac group received 30 mg of intravenous ketorolac 30 minutes before surgical incision, while the control group received normal saline. The post-operative analgesia was performed with a continuous infusion of tramadol at 12 mg/hour with the possibility of a 10 mg bolus every 10 minutes. Pain was assessed using the Visual Analog Scale (VAS), tramadol consumption and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16 and 24 hours post-operatively. We quantified times to rescue analgesic (morphine), adverse effects and patient satisfaction.

Description:

Damage to tissues has been shown to provoke a magnified reaction to noxious stimuli, peripherally by diminishing the threshold of nociceptive afferent nerve terminals and centrally by augmenting the excitability of second-order sensory neurons in the spinal cord; later resulting in an amplification and extension of postoperative pain after surgery. Hence, much research has focused on procedures to avoid these central neuroplastic changes through the usage of preemptive analgesia.

Experimental models have conducted to the idea of 'preemptive analgesia' . The decrement of afferent nociceptive inputs to the spinal cord using analgesic techniques started before the initial painful stimulus avoids or attenuates the formation of spinal hyperexcitabilty and avoids the transformed processing of afferent input, leading to less postoperative pain. Whether such experimental models are applicable to the noxious circumstances occurring during surgery is controversial.

Although preemptive analgesia with different agents have been successful in experimental animals, conclusions from human studies remain in conflict. A diversity of agents have been analyzed for their conceivable preemptive analgesic effects: local anesthetics, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, opioids, magnesium, cytokine synthesis inhibitors, ketamine, and tricyclic antidepressants.

Scientific research enabling an understanding of the molecular mechanisms of nociception has disclosed a considerable function of cytokines and prostaglandins (PG). Hyperexcitability also appears peripherally in nerve endings at the location of surgical tissue damage and is mediated in part by prostaglandins. Evidence is accumulating that products of the cyclooxygenase pathway may be engaged in the elaboration of central sensitization. Drugs that block the formation of prostaglandins such as NSAIDs might therefore be assumed to avoid or minimize the formation of this peripheral and central hyperexcitability. Their central analgesic actions are effected by averting spinal prostaglandin synthesis and attenuating liberation of neurotransmitters from the primary afferent terminals and spinal interneurons.

Sporadic studies have established some considerable preemptive benefit of NSAIDs. As a result, the objective of this study was to ascertain the impact of a NSAID, ketorolac, on pain severity and analgesic requirement, in the early postoperative period.

Ketorolac is a nonselective NSAID that blocks cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) enzymes and as a result blocks the formation of prostaglandins attenuating the sensitization procedures. The antinociceptive and anti-inflammatory action of NSAIDs may be associated to the suppression of nitric oxide synthase activation, decreased generation of proinflammatory cytokines, and lipoxine activation. Consequently, this multidirectional activity indicates that there may be the probability of adjusting the nociception process by the employment of these drugs perioperatively.

To our knowledge, no prior controlled study has determined the effectiveness of preoperative intravenous ketorolac compared to placebo in patients who underwent abdominal hysterectomies. Thus, this clinical trial was conceived to explore the postoperative analgesic efficiency and opioid-sparing action of a single dose of intravenous ketorolac in contrast with placebo administered preoperatively.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: November 2001
• Est. primary completion date: October 2001
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• normal height and weight

• ASA class I, II, III

• elective surgery

• surgery time between 30-150 min

• understanding of the Visual Analog Scale (VAS)

• no allergies or intolerance to NSAIDs or anesthetics

• no psychiatric illness.

Exclusion Criteria:

• renal deterioration

• history of peptic ulceration

• asthma

• coagulopathy

• cognitive impairment

• inability to use the Patient Controlled Analgesia (PCA) device

• history of chronic pain syndromes

• history of chronic use of analgesics, sedatives, opioids or steroids

• liver or hematologic disease

• a history of drug or alcohol abuse

• therapy with NSAIDs, anticoagulants, or lithium.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• Ketorolac Tromethamine
In the operating room, the anesthesiologist administered ketorolac (30 mg) in 50 mL of 0.9 % saline intravenously to patients in the ketorolac group 30 minutes before surgical incision (a single dose).

Other:
• Placebo
In the operating room, the anesthesiologist administered 50 mL of 0.9 % saline intravenously to patients in the control group 30 minutes before surgical incision

Locations

Country	Name	City	State
Spain	Complexo Hospitalario Arquitecto Marcide-Prof. Novoa Santos	Ferrol	A Coruña
United Kingdom	Oxford University Hospitals NHS Trust	Oxford	Oxfordshire

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Arquitecto Marcide

Countries where clinical trial is conducted

Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood Pressure (BP) systolic	Measured in mm Hg. We evaluated these hemodynamic parameters as an indirect measure of pain.	at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively	No
Other	Blood Pressure (BP) diastolic	Measured in mm Hg. We evaluated these hemodynamic parameters as an indirect measure of pain	at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively	No
Other	Heart rate	We evaluated these hemodynamic parameters as an indirect measure of pain	at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively	No
Other	Respiratory rate	We evaluated these hemodynamic parameters as an indirect measure of pain.	at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively	No
Other	Time for the first demand of analgesia	The time interval to first solicited rescue analgesia in the 24 h postoperatively (in minutes). This rescue analgesia was administered if the established analgesic treatment was not sufficient to alleviate pain.	24 h postoperatively.	No
Other	Number of rescue doses	The number of times a rescue analgesic dose was administered as a supplement in the first postoperative 24 hours.	24 h postoperatively	No
Other	Satisfaction score	Global patient satisfaction (0-3), regarding pain control, was measured 24 hours after the operation	24 hours postoperatively	No
Other	Side effects	Number of Participants with Serious and Non-Serious Adverse Events in the 24 hours postoperatively	24 hours postoperatively	No
Primary	Pain as measured by the Visual Analog Scale (VAS) score	The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).	at 0 hours postoperatively (arrival at recovery room)	No
Primary	Pain as measured by the Visual Analog Scale (VAS) score	The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).	at 1 hour postoperatively	No
Primary	Pain as measured by the Visual Analog Scale (VAS) score	The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).	at 2 hours postoperatively	No
Primary	Pain as measured by the Visual Analog Scale (VAS) score	The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).	at 4 hours postoperatively	No
Primary	Pain as measured by the Visual Analog Scale (VAS) score	The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).	at 8 hours postoperatively	No
Primary	Pain as measured by the Visual Analog Scale (VAS) score	The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).	at 12 hours postoperatively	No
Primary	Pain as measured by the Visual Analog Scale (VAS) score	The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).	at 16 hours postoperatively	No
Primary	Pain as measured by the Visual Analog Scale (VAS) score	The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).	at 24 hours postoperatively	No
Secondary	tramadol consumption	The cumulative amounts of tramadol (mg) administered through the Patient-Controlled-Analgesia (PCA) device as a basal infusion and the incremental supplemental bolus required by the patient were documented at these time points.	at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively	No