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Satisfactory Analgesia Minimal Emesis in Day Surgeries

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

Status
Completed
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02223377
Acronym
SAME-Day
Enrollment
402
Registered
2014-08-22
Start date
2015-01-01
Completion date
2019-03-01
Last updated
2026-06-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pain, Post Operative Nausea and Vomiting

Brief 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.

Detailed 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.

Interventions

DRUGMorphine

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)

DRUGHydromorphone

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)

Sponsors

McMaster University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Our Combined Primary Outcome Will be Number of Patients With Same Analgesia Minimal Emesis, as Compared Between the 2 Groups.At 2hrs or at the time of discharge from PACUOur 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.

Secondary

MeasureTime frameDescription
Number of Patients With Severe ItchingAt 2hrs or at the time of discharge from PACUSevere itching measured as visual analog scale score \> 5 on a 0-10 Visual Analog Scale, where 0 = no itching, and 10 = worst itching imaginable
Severe SedationAt 2hrs or at the time of discharge from PACURamsay Sedation Scale 0-6
Severe Respiratory DepressionAt 2hrs or at the time of discharge from PACUPresence of Respiratory Rate below 10 and/or Presence of Oxygen Saturation \<90
Patients Requesting Oral Analgesia in the Day Surgery UnitAt 2hrs or at the time of discharge from PACUUse of rescue drug for pain
Mean Dose of Analgesic Used5 hours post-admit to hospitalFor a day surgery case, from the time of hospital admittance to discharge from hospital is an average 5 hours.
Patient Satisfaction ScoreAt 5 hours post-admit to hospitalPatient satisfaction is measured on a 0-10 visual analogue scale, where 0=completely unsatisfied; 10=extremely satisfied
Time to Discharge From PACUAt 2hrs or at the time of discharge from PACUFor a day surgery case, from the time out of operating room to discharge from PACU is an average 2 hours.
Time to Discharge From HospitalAt 5 hours post-admit to hospitalFor a day surgery case, from the time of hospital admittance to discharge from hospital is an average 5 hours.

Countries

Canada

Contacts

PRINCIPAL_INVESTIGATORHarsha Shanthanna, MD

St. Joseph's Healthcare Hamilton/McMaster University

PRINCIPAL_INVESTIGATORJames Paul, MD

Hamilton Health Sciences/McMaster University

Participant flow

Participants by arm

ArmCount
Morphine
Analgesia with equipotent doses of Morphine and Hydromorphone will be administered in titrated doses. Doses are 1ml=1mg of morphine or 0.2 mg of hydromorphone. Potency ratio of 1:5 (M: HM). 0.05mg/kg morphine units (rounding off to the nearest 1 ml or 0.5 ml) Morphine: Participant to be asked for their pain score, and if it is more than 4 out of 10 (NAS): to receive the 1st dose within 5 minutes after coming to PACU: 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. 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)
199
Hydromorphone
Analgesia with equipotent doses of Morphine and Hydromorphone will be administered in titrated doses. Doses are 1ml=1mg of morphine or 0.2 mg of hydromorphone. Potency ratio of 1:5 (M: HM). 0.05mg/kg morphine units (rounding off to the nearest 1 ml or 0.5 ml) Hydromorphone: Participant to be asked for their pain score, and if it is more than 4 out of 10 (NAS): to receive the 1st dose within 5 minutes after coming to PACU: 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. 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)
203
Total402

Baseline characteristics

CharacteristicMorphineHydromorphoneTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
17 Participants28 Participants45 Participants
Age, Categorical
Between 18 and 65 years
182 Participants175 Participants357 Participants
Age, Continuous46.1 years
STANDARD_DEVIATION 13.8
47.1 years
STANDARD_DEVIATION 14
46.6 years
STANDARD_DEVIATION 13.9
Anxiety score6 units on a scale6 units on a scale6 units on a scale
Apfel score2.6 units on a scale
STANDARD_DEVIATION 0.9
2.5 units on a scale
STANDARD_DEVIATION 1
2.6 units on a scale
STANDARD_DEVIATION 0.9
Body Mass Index (BMI)27.55 kg/m^2
STANDARD_DEVIATION 4
27.06 kg/m^2
STANDARD_DEVIATION 4.27
27.37 kg/m^2
STANDARD_DEVIATION 4.14
Catastrophising score9 units on a scale10 units on a scale9 units on a scale
Chronic pain in other areas35 Participants33 Participants68 Participants
Depression score2 units on a scale2 units on a scale2 units on a scale
Preoperative pain in the operative area83 Participants83 Participants166 Participants
Race and Ethnicity Not Collected0 Participants
Region of Enrollment
Canada
199 Participants203 Participants402 Participants
Sex: Female, Male
Female
132 Participants126 Participants258 Participants
Sex: Female, Male
Male
67 Participants77 Participants144 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 1990 / 202
other
Total, other adverse events
7 / 19913 / 202
serious
Total, serious adverse events
11 / 19910 / 202

Outcome results

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.

Time frame: At 2hrs or at the time of discharge from PACU

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
MorphineOur Combined Primary Outcome Will be Number of Patients With Same Analgesia Minimal Emesis, as Compared Between the 2 Groups.172 Participants
HydromorphoneOur Combined Primary Outcome Will be Number of Patients With Same Analgesia Minimal Emesis, as Compared Between the 2 Groups.175 Participants
p-value: 0.99795% CI: [0.56, 1.78]Regression, Logistic
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.

Time frame: 5 hours post-admit to hospital

ArmMeasureValue (MEAN)Dispersion
MorphineMean Dose of Analgesic Used5.7 Equivalent morphine unitStandard Deviation 3.9
HydromorphoneMean Dose of Analgesic Used4.9 Equivalent morphine unitStandard Deviation 3.3
p-value: 0.0495% CI: [-1.43, -0.03]ANOVA
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

Time frame: At 2hrs or at the time of discharge from PACU

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
MorphineNumber of Patients With Severe Itching2 Participants
HydromorphoneNumber of Patients With Severe Itching5 Participants
Secondary

Patient Satisfaction Score

Patient satisfaction is measured on a 0-10 visual analogue scale, where 0=completely unsatisfied; 10=extremely satisfied

Time frame: At 5 hours post-admit to hospital

ArmMeasureValue (MEAN)Dispersion
MorphinePatient Satisfaction Score9.1 score on a scaleStandard Deviation 1.8
HydromorphonePatient Satisfaction Score9.3 score on a scaleStandard Deviation 1.2
Secondary

Patients Requesting Oral Analgesia in the Day Surgery Unit

Use of rescue drug for pain

Time frame: At 2hrs or at the time of discharge from PACU

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
MorphinePatients Requesting Oral Analgesia in the Day Surgery Unit128 Participants
HydromorphonePatients Requesting Oral Analgesia in the Day Surgery Unit135 Participants
Secondary

Severe Respiratory Depression

Presence of Respiratory Rate below 10 and/or Presence of Oxygen Saturation \<90

Time frame: At 2hrs or at the time of discharge from PACU

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
MorphineSevere Respiratory Depression11 Participants
HydromorphoneSevere Respiratory Depression10 Participants
Secondary

Severe Sedation

Ramsay Sedation Scale 0-6

Time frame: At 2hrs or at the time of discharge from PACU

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
MorphineSevere Sedation5 Participants
HydromorphoneSevere Sedation8 Participants
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.

Time frame: At 5 hours post-admit to hospital

ArmMeasureValue (MEAN)Dispersion
MorphineTime to Discharge From Hospital3.2 HoursStandard Deviation 1.1
HydromorphoneTime to Discharge From Hospital3.3 HoursStandard Deviation 1.1
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.

Time frame: At 2hrs or at the time of discharge from PACU

ArmMeasureValue (MEAN)Dispersion
MorphineTime to Discharge From PACU91.2 MinutesStandard Deviation 58.6
HydromorphoneTime to Discharge From PACU92.8 MinutesStandard Deviation 50.6

Source: ClinicalTrials.gov · Data processed: Jun 24, 2026