Intraoperative Administration of Intravenous Morphine in Patients Undergoing Laparoscopic Cholecystectomy - a Retrospective, Observational, Quality-improvement Study
Conditions: Postoperative Pain, Morphine, Laparoscopic Cholecystectomy
Sponsor: Esbjerg Hospital - University Hospital of Southern Denmark

1 
 
Coverpage: 
 
Official title of the study: 
Intraoperative administration of intravenous morphine in patients undergoing 
laparoscopic cholecystectomy – a retrospective, observational, quality-
improvement study. 
 
Document date: 
 
November 21st 2023 
 
NCT number: 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
 
 
 
Purpose: 
Primary purpose: To investigate whether intraoperatively administered morphine 
improves postoperative analgesia. 
Secondary purpose: To investigate whether intraoperatively administered morphine 
increases opioid related adverse effects. 
PICO: 
Population:  adult patients who have undergone elective laparoscopic 
cholecystectomy 
Intervention: change in anesthesia technique to include an intraoperative 
dose of morphine 
Comparison:  
A) no morphine = patients operated in the year 
before the change in anesthesia protocol (June 
1st 2022 – May 31st 2023) 
B) morphine = patients operated in the year 
following the change in anesthesia protocol 
(Jan 1st 2024 – Dec 31st 2024) 
Outcomes: 
Primary: use of rescue analgesia in the postoperative ward 
 
Secondary: pain scores on admittance and discharge from 
postoperative ward, time from end of surgery to admittance 
to postoperative ward (surrogate measure for emergence 
from anesthesia), use of rescue antiemetic treatment in the 
postoperative ward, time in postoperative ward, use of 
analgesic and antiemetic treatment in the first 24 hours after 
discharge from postoperative ward, time in hospital. 
Background: 
Pain following laparoscopic cholecystectomy is complex and stems from several stimuli: 
e.g. skin-incisions, abdominal distention due to pneumoperitoneum and irritation of the 
phrenic nerve.1 Postoperative pain continues to be a problem despite years of focus on 
the issue as well as increased use of laparoscopic and minimally invasive, surgical 
technique. This holds true for laparoscopic cholecystectomy as well. 2,3 Some 
investigators report that as much as 50-70% of patients experience moderate to 
intensive pain postoperatively. 4 It is well known that postoperative pain causes 
increased morbidity and is a primary cause of prolonged length of hospital stay.1 
Multimodal analgesic approach is recommended for this type of surgery. Because use of 
opioids frequently cause adverse effects an opioid-sparing approach is recommended.2 
However, non-opioid analgesia also has the potential for adverse effects. Even if it is 
possible to perform opioid-free anesthesia knowledge and evidence is still sparse, and 
peri- and postoperative opioid rescue analgesia is often necessary.5,6,7 

3 
 
We hypothesize, that multimodal analgesia including a perioperative dose of morphine 
(0,1 mg/kg) given 20 minutes after start of surgery will have beneficial effect on 
postoperative pain without causing significant increase in opioid related adverse effects. 
Design: 
 
Retrospective, observational, data from patient records/register based 
 
Investigation site: Hospital of South West Jutland Esbjerg 
 
Population: 
2 groups: 
a) No morphine intraoperatively: Patients operated in the year before 
change in anesthesia protocol 
b) Morphine intraoperatively: Patients operated in the year after change 
in anesthesia protocol 
 
 
 
Inclusion criteria: 
- 
Patient having undergone elective laparoscopic 
cholecystectomy 
 
 
Exclusion criteria: 
- 
Age under 21 (because these patients are admitted to a 
separate ward for children and young adults) 
- 
Patients who are unable to give consent to anesthesia 
- 
Patients who cannot participate in pain-scoring by 
numerical ranking scale (NRS) 
- 
Patients with chronic pain (characterized by patient 
receiving regular analgesic treatment and patients with 
active or previous contact to pain clinic) 
- 
Patients with active or previous substance abuse 
- 
Emergency surgery 
Outcomes 
Primary: 
- 
Use of rescue analgesia (calculation of total morphine 
equivalents) in the postoperative ward 
Secondary: 
- 
Intraoperative opioid use (calculation of total morphine 
equivalents) 
- 
Time from end of operation to admittance to 
postoperative ward (surrogate measure of emergence 
from anesthesia) 
- 
Pain score at admittance to postoperative ward, scale 
from 0 to 3* 
- 
Pain score at discharge from postoperative ward, scale 
from 0 to 3* 

4 
 
*Due to retrospective, register based design 
we cannot use standard numerical ranking 
scale (NRS), since local practice is to register 
pain in intervals of NRS: no pain = 0, light pain 
= 1-3, moderate pain = 4-6, severe pain = 7-10 
- 
Use of rescue antiemetic treatment in the postoperative 
ward 
- 
Time in postoperative ward 
- 
Analgesic use in surgical ward during first 24 hours if 
admitted** 
- 
Use of antiemetic treatment in surgical ward during first 
24 hours if admitted** 
** It is expected that a large proportion of the 
included patients will be managed as out-
patients.  
- 
Total admission time. 
 
Other data collected for statistical analysis: 
- 
Age at operation 
- 
Gender 
- 
ASA-classification 
- 
Co-morbidity 
- 
Height 
- 
Weight 
- 
Smoking habits (smoker/non-smoker) 
- 
Use of alcohol (none, 1-21 units per week, > 21 units per 
week) 
- 
In-patient/out-patient status 
- 
Anesthesia maintenance (intravenous or inhalational)’ 
- 
Dose of fentanyl, remifentanil and morphine 
- 
Use of lidocaine 
- 
Postoperative nausea and vomiting (PONV)-prophylaxis 
- 
Use of vasopressor or inotropes 
- 
Paracetamol and/or NSAIDs gives preoperatively or 
intraoperatively 
- 
Pre- and postoperative C-reactive protein (CRP)-values, 
if taken 
Analyses: 
- 
Per protocol 
o a) No-morphine vs b) Morphine 
o T-test, statistical difference in: 
 
Analgesic use in postoperative ward 
(primary) 
 
Intraoperative analgesic use 
 
Pain scores in postoperative ward  
 
Time for end of surgery to admittance to 
postoperative ward 

5 
 
 
Use of rescue antiemetic drugs in 
postoperative ward 
 
Time in postoperative ward 
 
Use of opioid analgesia and antiemetic 
drugs in surgical ward 
 
Time in hospital 
o If necessary and possible logistic regression 
analyses. 
Anticipated time schedule: 
2023 
Protocol, permissions and generation of data collection tool 
in Redcap 
 
Feb - Sept 2024 
Data collection, no-morphine group 
 
Oct 2024 – April 2025 
Data collection, morphine group 
 
April 2025 - ?  
Data management, analyses, manuscript, publication 
 
 
Ethics: 
Patients are all subject to standard anesthesia care as per the department guidelines (as 
per approved anesthesia protocol). No experimental drugs or techniques are used. 
Written consent to access relevant patient files without direct consent from each patient 
as per the quality improvement nature of the study has been obtained. 
We have consulted our local board of directors (approval date October 28th 2023, Acadre 
case no 23/47526) as well as the regional ethics committee (approval date July 3rd 2023, 
case no S-20232000-86). 
Perspective: 
Laparoscopic cholecystectomy is a frequent procedure. Despite wide attention to the 
problem, patients undergoing this procedure is still experience considerable 
postoperative pain. We believe that our findings will improve knowledge in pain 
management and as such be of benefit to future patients 
Bibliography: 
 
1 Jiang B, Song Y. Pharmacotherapeutic pain management in patients undergoing laparoscopic 
cholecystectopmy. Adv Clin Exp Med 2022; 31(11): 1275-1288. 
 
2 Barazanchi AW, MacFater WS, Rahiri J-L et al. Evidence-based management of pain after 
laparoscopic cholecystectomy: a PROSPECT review update. Br J Anaesth 2018; 121(4): 787-
803. 
 
3 Rosero EB, Joshi GP. Hospital readmission after ambulatory laparoscopic cholecystectomy: 
incidence and predictors. J Surg Res 2017; 219: 108-115. 
 
                                              

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4 Li J, Wang G, Xu W et al. Efficacy of intravenous lidocaine om pain relief in patients 
undergoing laparoscopic cholecystectomy: A meta-analysis from randomized controlled trials. 
Int j Surg 2018; 50: 137-145. 
 
5 Bakan M, Umutoglu T, Topuz U et al. Opioid-freee intravenous anesthesia with propofol, 
dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, 
randomized, double-blinded study. Braz J Anesthesiol 2015; 65(3): 191-199. 
 
6 Magoon R, Choudhury A. Opioid free anesthesia: is it too early to bid adieu? Can J Anesth 
2019; 66(10): 1268-1269. 
 
7 De Oliveira Jr GS. Is there a strong link between intraoperative anesthetic management and 
postoperative recovery? J Clin Anesth 2019; 53: 81-82.