Satisfactory Analgesia Minimal Emesis in Day Surgeries

Pain Clinical Trial

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Official title:

Most Effective Opioid Analgesia in Ambulatory Surgeries: a Randomized Control, Investigator Blinded, Parallel Group With Superiority Design Study of Morphine Versus Hydromorphone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02223377
• Other study ID #: 14-482
• Secondary ID: CAS-2014-038
• Status: Completed
• Phase: N/A
• Start date: January 2015
• Est. completion date: March 2019

Study information

• Verified date: March 2023
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Currently nearly 70% or more surgeries are being done as ambulatory (day care) procedures as they offer significant benefit to the patients as well as to the hospitals. Inadequate pain relief (30%-40%) and nausea-vomiting form the leading factors affecting the quality of care and hence its efficiency. Opioids form the primary modality to treat moderate to severe pain, but can also cause significant nausea-vomiting and other side effects. Although hydromorphone is five times more potent than morphine, in equianalgesic doses they both could provide similar pain relief. They both exert no ceiling effect for their analgesia, and hence incomplete or inadequate analgesia is related to the appearance of side effects. In this study the investigators shall assess the proportion of patients who satisfy the outcome of 'satisfactory analgesia with minimal nausea-vomiting' in ambulatory surgeries, assessed at 2 hours after surgery. Patients would be randomized to receive either morphine or hydromorphone in the surgical recovery area. All personnel involved with the study would be blinded. The investigators will also look to assess the time to discharge and other side effects. This will help to choose the better drug, thereby improving pain relief and side effects, and also the efficiency of health care delivery.

Description:

There has been an exponential increase in the number of day case surgical procedures also called as ambulatory surgeries (AS), over the last 2 years.(1) Currently around 70% of procedures are being done as AS, with known benefits to patients and hospitals.(2) Its efficiency and cost effectiveness depends upon its organization and delivery of services. Pain and PONV are recognized as the leading factors affecting the quality of services delivered under AS,(1,3) and they affect the recovery, discharge, and overall satisfaction of patients.(4,5) According to literature, postsurgical pain could be inadequately treated in 30%-60% of patients and 30%-40% of AS patients suffer from significant PONV.(3,6,7) It is estimated that a single episode of PONV can prolong the PACU stay by 25 mins,(8) and patients rate PONV to be the most undesirable outcome associated with anesthesia.(4) Despite the increasing use of non-opioid analgesics, opioid analgesics have remained the primary modality in moderate to severe pain.(7) They cause several side effects such as drowsiness, sedation, PONV, itching and respiratory depression. Appropriate selection of opioid medications becomes significantly important to deliver safe and effective analgesia with minimal side effects. Although M has been the most commonly used medication, HM is also being increasingly used.(9) We do not yet know whether HM is more effective than M in AS patients. Both M and HM exert no ceiling effect for their analgesia, and by this nature incomplete or inadequate analgesia is related to the appearance of side effects.(10) Hence clinical effectiveness of opioids, relative to each other, is reflected not just by satisfactory analgesia, but by a combination of 'satisfactory analgesia with limited side effects'. Clinical observation suggests that HM is clinically better by providing superior or equivalent analgesia with decreased side effects.(9) HM is a semi-synthetic morphine derivative that differs from M in its position 6 of the benzol ring, where it has a keto-group instead of a hydroxy group, making it 5-10 times more potent and enhances its distribution to cerebral tissues, making for easier titration.(9) The t1/2 Ke0 (transfer life from plasma to effect site) is 1.6hr - 4 hr for M, compared to 18-38 min for HM.(9,10) It is observed that health care providers may be willing to provide higher dose of HM compared to M in EMU, as its actual quantity of drug is much smaller and therefore appears to cause less concern.(12, 13) Our literature review showed that there are no previous studies comparing these 2 medications in AS patients. The lone systematic review compared various acute and chronic pain studies, in various routes of drug administration.(9) Of the 11 studies identified; only 4 were done in acute pain settings.(13-16) Two of them were done by the same author in ER settings. Chang et al noted that HM reduced the mean pain scores by 1.3 units [95% CI= (-2.2 to -0.5)] compared to M in 198 adults treated in ER.(12,13). However it did not show much difference in geriatric population.14 In perioperative settings, Hong et al studied the difference in nausea between the 2 medications in 50 patients using PCA and found no difference.(15) Rapp et al studied various effects between the 2 medications in 61 surgical patients using PCA. There is not much clarity about their primary outcome; however they found the effects to be similar.(16) Both these studies had smaller sample sizes. The meta-analysis performed demonstrated that the HM does provide better analgesia than M, with a small effect size; Cohen's d=0.266 (p=0.012).(9) Looked at acute pain alone it was statistically significant (p=0.006), compared to chronic pain (p=0.889). It was noted that that there is a definite lack of comparative studies between them in surgical settings.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 402
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• ambulatory surgeries producing at least moderate pain-such as cholecystectomy, appendicectomy, ovarian cystectomy, inguinal hernia repair, abdominal wall hernias

• ability to communicate in English.

Exclusion Criteria:

• allergy to M or HM

• patient on regular chronic opioid medication

• patient uncontrolled systemic disease

• severe obesity with a BMI >35

• significant psychological impairment

• history of drug addiction or dependence

• any planned regional or nerve block other than local anesthesia infiltration patients with confirmed sleep apnea

• emergency surgeries and urological surgeries

Related Conditions & MeSH terms

• Pain
• Post Operative Nausea and Vomiting
• Postoperative Nausea and Vomiting
• Vomiting

Intervention

Drug:
• Morphine
1st dose: syringe of 0.04mg/kg morphine units (rounding off to the nearest 1 ml or 0.5 ml); with a maximum of 3 mg of morphine equivalents is administered. Repeat doses: 0.02 mg/kg morphine units every 5-10 minutes to titrate for analgesia and side effects (rounding off to the nearest 1 ml or 0.5 ml)
• Hydromorphone
1st dose: syringe of 0.04mg/kg morphine units (rounding off to the nearest 1 ml or 0.5 ml); with a maximum of 3 mg of morphine equivalents is administered. Repeat doses: 0.02 mg/kg morphine units every 5-10 minutes to titrate for analgesia and side effects (rounding off to the nearest 1 ml or 0.5 ml)

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (7)

Chatterjee S, Rudra A, Sengupta S. Current concepts in the management of postoperative nausea and vomiting. Anesthesiol Res Pract. 2011;2011:748031. doi: 10.1155/2011/748031. Epub 2011 Nov 3. — View Citation

Felden L, Walter C, Harder S, Treede RD, Kayser H, Drover D, Geisslinger G, Lotsch J. Comparative clinical effects of hydromorphone and morphine: a meta-analysis. Br J Anaesth. 2011 Sep;107(3):319-28. doi: 10.1093/bja/aer232. Epub 2011 Aug 5. — View Citation

Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg. 1999 Sep;89(3):652-8. doi: 10.1097/00000539-199909000-00022. — View Citation

Sarin P, Philip BK, Mitani A, Eappen S, Urman RD. Specialized ambulatory anesthesia teams contribute to decreased ambulatory surgery recovery room length of stay. Ochsner J. 2012 Summer;12(2):94-100. — View Citation

Shnaider I, Chung F. Outcomes in day surgery. Curr Opin Anaesthesiol. 2006 Dec;19(6):622-9. doi: 10.1097/ACO.0b013e328010107e. — View Citation

Troy AM, Cunningham AJ. Ambulatory surgery: an overview. Curr Opin Anaesthesiol. 2002 Dec;15(6):647-57. doi: 10.1097/00001503-200212000-00008. — View Citation

White PF. Pain management after ambulatory surgery - where is the disconnect? Can J Anaesth. 2008 Apr;55(4):201-7. doi: 10.1007/BF03021503. No abstract available. English, French. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Our Combined Primary Outcome Will be Number of Patients With Same Analgesia Minimal Emesis, as Compared Between the 2 Groups.	Our combined primary outcome will be number of patients with SAME, as compared between the 2 groups. Analgesia will be based on Numerical Analogue Scale for Pain 0-10 (appendix 3), and Post-operative nausea and vomiting will be based on Verbal Descriptive Scale 0-5 (appendix 3). These observations will be made at the end of 2 hrs or before (corresponding to the time of discharge from PACU), by the PACU nurse.	At 2hrs or at the time of discharge from PACU
Secondary	Number of Patients With Severe Itching	Severe itching measured as visual analog scale score > 5 on a 0-10 Visual Analog Scale, where 0 = no itching, and 10 = worst itching imaginable	At 2hrs or at the time of discharge from PACU
Secondary	Severe Sedation	Ramsay Sedation Scale 0-6	At 2hrs or at the time of discharge from PACU
Secondary	Severe Respiratory Depression	Presence of Respiratory Rate below 10 and/or Presence of Oxygen Saturation <90	At 2hrs or at the time of discharge from PACU
Secondary	Patients Requesting Oral Analgesia in the Day Surgery Unit	Use of rescue drug for pain	At 2hrs or at the time of discharge from PACU
Secondary	Mean Dose of Analgesic Used	For a day surgery case, from the time of hospital admittance to discharge from hospital is an average 5 hours.	5 hours post-admit to hospital
Secondary	Patient Satisfaction Score	Patient satisfaction is measured on a 0-10 visual analogue scale, where 0=completely unsatisfied; 10=extremely satisfied	At 5 hours post-admit to hospital
Secondary	Time to Discharge From PACU	For a day surgery case, from the time out of operating room to discharge from PACU is an average 2 hours.	At 2hrs or at the time of discharge from PACU
Secondary	Time to Discharge From Hospital	For a day surgery case, from the time of hospital admittance to discharge from hospital is an average 5 hours.	At 5 hours post-admit to hospital