Clinical Trial of the Use of Intraperitoneal Local Anaesthetic

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00180687
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 4
• Duration (Months): 11
• Patients Per Site Per Month: 7.3

Study Details

Study Description

Brief Summary

Patients undergoing keyhole gall bladder removal will be divided into 3 groups, one control, one will have local anaesthetic and the third will have normal saline nebulised into their abdomen before closure of the wounds to reduce postoperative pain. These medications will be given on top of the standard pain management protocol.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative	Drug: Nebulised Bupivacaine intraperitoneally; Drug: Normal Saline; Drug: Injected Bupivacaine intraperitoneally; Other: No Intraperitoneal Therapeutics	Phase 3

Detailed Description

Pain post laparoscopic procedures can be divided into access related, operation site and distension related. The access type can be attenuated by the use of sub dermal infiltration of local anaesthetic and rarely causes significant discomfort. It has been advocated that placement of a peritoneal gas drain significantly reduces postoperative pain particularly referred to the shoulder tip. Realistically, however, if attention is paid to expelling the residual gas at the end of the procedure this complication is rarely problematic. Operative site pain however is more difficult to manage. In limited gynaecological procedures it has been shown that local installation of local anaesthetic decreased the analgesic requirement of patients post operatively. These observations would not be as transferable to more extensive colorectal or solid organ surgery as the amount of local anaesthesia required would be toxic to the patient. Use of the nebuliser, however maybe able to alleviate pain by efficiently using the dosage required.

This is a prospective randomised double blind trial. Sixty patients will be allocated randomly between three groups, 20 patients in each group:

1. Control group

2. Nebulised intraperitoneal local anaesthetic (Bupivacaine 0.25%, 3mg/Kg)

3. Nebulised intraperitoneal normal saline Ward staff will be blinded to which group the patients are in. All patients undergoing laparoscopic cholecystectomy who have given written, informed consent are eligible for inclusion. Patients with local anaesthetics allergy and patients whom pain evaluation is considered unreliable due to chronic opiate use or neurological diseases are excluded.

No pre-medication is to be given and a standardised anaesthetic technique is to be employed for all patients.

Standard 4 ports technique for laparoscopic cholecystectomy will be used with intraperitoneal pressure between 12-14 mmHg. This will be achieved using CO2 as the insufflation gas.

The local anaesthetic (approximately 10mls) will be delivered via a fine sterile catheter that will be inserted via the epigastric port under direct vision at the end of the procedure. Afterward the pneumoperitoneum will be deflated and the wound will be closed and subcutaneous local anaesthetic will be injected in and around the wounds.

Postoperatively, all the patients will have PCA as the main analgesia supported by NSAIDs unless contraindicated. Patients will eat and drink as desired and drips will be taken as soon as it is safe to do so.

Postoperative pain scoring will be stared in recovery and continue on the wards using the visual analogue scale.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Prospective Double Blind Randomized Controlled Trial of the Use of Intraperitoneal Nebulised Local Anaesthetic
• Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Sep 1, 2005
• Actual Study Completion Date: Sep 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Control No intraperitoneal therapeutics (No nebulised Bupivacaine)	Other: No Intraperitoneal Therapeutics; No Intraperitoneal Therapeutics given
Placebo Comparator: IP Aerosolized Normal Saline Intraperitoneal nebulised 10mls. Normal Saline (No nebulised Bupivacaine)	Drug: Normal Saline; Nebulised Normal Saline; Other Names: 0.9 % Normal Saline
Experimental: Nebulised Bupivacaine intraperitoneally Intraperitoneal Nebulised 10mls. Bupivacaione (Marcaine)	Drug: Nebulised Bupivacaine intraperitoneally; Nebulised Marcaine (Bupivacaine); Other Names: Marcaine
Active Comparator: Injected Bupivacaine intraperitoneally Intraperitoeal Injected 10 mls.Bupivacaine (Marcaine) (No nebulised Bupivacaine)	Drug: Injected Bupivacaine intraperitoneally; Injected Marcaine directly into the peritoneal cavity; Other Names: Marcaine

Outcome Measures

Primary Outcome Measures

1. Reduction in Postoperative Pain [0 hours, 6 hours, 12 hours, 24 hours]

   Postoperative pain was measured using Pain scale 0-10 (0 = No Pain, 10 = Maximum pain). A trained nursing staff will ask the patient about his / her pain and document that correctly in the chart. The staff will also document if the patient requires any analgesia, the type and the dose.

Secondary Outcome Measures

1. Number of Vomiting / Nausea Episodes [24 hours]

   Nausea and vomiting are known adverse effect of opioids usage. By reducing the use of opioids we can reduce or abolish these side effect which will enhance early patient recovery and discharge and reduce hospital cost. We will measure the number of episodes when the patient suffers from these side effect and correlate them with opioids use.

2. Hours Needed for Safe Mobilization [24 Hours]

   Drowsiness and delayed mobilization are known adverse effect of opioids usage. By reducing the use of opioids we can reduce or abolish these side effect which will enhance early patient recovery and discharge and reduce hospital cost. We will measure how many hours will take the patient to mobilize freely and safely and correlate them with opioids use.

3. Postoperative Morphine Use [24 Hoiurs]

   The reduction in cost comes from reducing the use of opioid which requires nursing supervision and also special pump to be delivered as in the cases of patient controlled analgesia. With that reduction, there will be a reduction in opioid related adverse events that mandate medical or nursing attention and prolong hospitalization, these adverse events include nausea and vomiting, delay mobilization due to drowsiness and alter mental status caused by opioid usage. For these reasons we are collecting data related to these adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• All they patients undergoing laparoscopic cholecystectomy will be included.

Exclusion Criteria:

• Patients with local anaesthetic allergy, patients on chronic opiate medication or those with neurological diseases that make pain evaluation unreliable will be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Mary's Hospital	London		United Kingdom	W2 1NY

Sponsors and Collaborators

• Imperial College London

Investigators

• Principal Investigator: Nawar A Alkhamesi, MD, PhD, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nawar Alkhamesi, Clinical Research Fellow, Imperial College London
• ClinicalTrials.gov Identifier: NCT00180687
• Other Study ID Numbers: 02.CD/218E; Dr. David Peck; Prof. Sir Ara Darzi
• First Posted: Sep 16, 2005
• Last Update Posted: Sep 15, 2015
• Last Verified: Aug 1, 2015

• Keywords provided by Nawar Alkhamesi, Clinical Research Fellow, Imperial College London: Pain; Nebulisation; Cholecystectomy; Laparoscopic; Bupivacaine; Local Anaesthetic
• Additional relevant MeSH terms: Pain, Postoperative; Bupivacaine; Coal Tar

Study Results

Participant Flow

Arm/Group Title	Control	IP Aerosolized Normal Saline	Nebulised Bupivacaine Intraperitoneally	Injected Bupivacaine Intraperitoneally
Arm/Group Description	No intraperitoneal therapeutics (No nebulised Bupivacaine) No Intraperitoneal Therapeutics: No Intraperitoneal Therapeutics given	Intraperitoneal nebulised 10mls. Normal Saline (No nebulised Bupivacaine) Normal Saline: Nebulised Normal Saline	Intraperitoneal Nebulised 10mls. Bupivacaione (Marcaine) Nebulised Bupivacaine intraperitoneally: Nebulised Marcaine (Bupivacaine)	Intraperitoeal Injected 10 mls.Bupivacaine (Marcaine) (No nebulised Bupivacaine) Injected Bupivacaine intraperitoneally: Injected Marcaine directly into the peritoneal cavity
Period Title: Overall Study
STARTED	20	20	20	20
COMPLETED	20	20	20	20
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Control	IP Aerosolized Normal Saline	Nebulised Bupivacaine Intraperitoneally	Injected Bupivacaine Intraperitoneally	Total
Arm/Group Description	No intraperitoneal therapeutics (No nebulised Bupivacaine) No Intraperitoneal Therapeutics: No Intraperitoneal Therapeutics given	Intraperitoneal nebulised 10mls. Normal Saline (No nebulised Bupivacaine) Normal Saline: Nebulised Normal Saline	Intraperitoneal Nebulised 10mls. Bupivacaione (Marcaine) Nebulised Bupivacaine intraperitoneally: Nebulised Marcaine (Bupivacaine)	Intraperitoeal Injected 10 mls.Bupivacaine (Marcaine) (No nebulised Bupivacaine) Injected Bupivacaine intraperitoneally: Injected Marcaine directly into the peritoneal cavity	Total of all reporting groups
Overall Participants	20	20	20	20	80
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	47.65	47.65	51.60	48.70	49
Sex: Female, Male (Count of Participants)
Female	16 80%	18 90%	17 85%	18 90%	69 86.3%
Male	4 20%	2 10%	3 15%	2 10%	11 13.8%
Region of Enrollment (participants) [Number]
United Kingdom	20 100%	20 100%	20 100%	20 100%	80 100%

Outcome Measures

1. Primary Outcome

Title	Reduction in Postoperative Pain
Description	Postoperative pain was measured using Pain scale 0-10 (0 = No Pain, 10 = Maximum pain). A trained nursing staff will ask the patient about his / her pain and document that correctly in the chart. The staff will also document if the patient requires any analgesia, the type and the dose.
Time Frame	0 hours, 6 hours, 12 hours, 24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	IP Aerosolized Normal Saline	Nebulised Bupivacaine Intraperitoneally	Injected Bupivacaine Intraperitoneally
Arm/Group Description	No intraperitoneal therapeutics (No nebulised Bupivacaine) No Intraperitoneal Therapeutics: No Intraperitoneal Therapeutics given	Intraperitoneal nebulised 10mls. Normal Saline (No nebulised Bupivacaine) Normal Saline: Nebulised Normal Saline	Intraperitoneal Nebulised 10mls. Bupivacaione (Marcaine) Nebulised Bupivacaine intraperitoneally: Nebulised Marcaine (Bupivacaine)	Intraperitoeal Injected 10 mls.Bupivacaine (Marcaine) (No nebulised Bupivacaine) Injected Bupivacaine intraperitoneally: Injected Marcaine directly into the peritoneal cavity
Measure Participants	20	20	20	20
Pain in Recovery (0 Hours)	9.2	10	3.3	9.3
Pain at 6 hours	8.2	8.1	0.7	7.2
Pain at 12 hours	7.9	8	0.6	6.7
Pain at 24 hours	6.1	6.2	0.5	5.6

2. Secondary Outcome

Title	Number of Vomiting / Nausea Episodes
Description	Nausea and vomiting are known adverse effect of opioids usage. By reducing the use of opioids we can reduce or abolish these side effect which will enhance early patient recovery and discharge and reduce hospital cost. We will measure the number of episodes when the patient suffers from these side effect and correlate them with opioids use.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	IP Aerosolized Normal Saline	Nebulised Bupivacaine Intraperitoneally	Injected Bupivacaine Intraperitoneally
Arm/Group Description	No intraperitoneal therapeutics (No nebulised Bupivacaine) No Intraperitoneal Therapeutics: No Intraperitoneal Therapeutics given	Intraperitoneal nebulised 10mls. Normal Saline (No nebulised Bupivacaine) Normal Saline: Nebulised Normal Saline	Intraperitoneal Nebulised 10mls. Bupivacaione (Marcaine) Nebulised Bupivacaine intraperitoneally: Nebulised Marcaine (Bupivacaine)	Intraperitoeal Injected 10 mls.Bupivacaine (Marcaine) (No nebulised Bupivacaine) Injected Bupivacaine intraperitoneally: Injected Marcaine directly into the peritoneal cavity
Measure Participants	20	20	20	20
Mean (Full Range) [Number of vomitting / Nausea episodes]	7.1	7.1	2	6.8

3. Secondary Outcome

Title	Hours Needed for Safe Mobilization
Description	Drowsiness and delayed mobilization are known adverse effect of opioids usage. By reducing the use of opioids we can reduce or abolish these side effect which will enhance early patient recovery and discharge and reduce hospital cost. We will measure how many hours will take the patient to mobilize freely and safely and correlate them with opioids use.
Time Frame	24 Hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	IP Aerosolized Normal Saline	Nebulised Bupivacaine Intraperitoneally	Injected Bupivacaine Intraperitoneally
Arm/Group Description	No intraperitoneal therapeutics (No nebulised Bupivacaine) No Intraperitoneal Therapeutics: No Intraperitoneal Therapeutics given	Intraperitoneal nebulised 10mls. Normal Saline (No nebulised Bupivacaine) Normal Saline: Nebulised Normal Saline	Intraperitoneal Nebulised 10mls. Bupivacaione (Marcaine) Nebulised Bupivacaine intraperitoneally: Nebulised Marcaine (Bupivacaine)	Intraperitoeal Injected 10 mls.Bupivacaine (Marcaine) (No nebulised Bupivacaine) Injected Bupivacaine intraperitoneally: Injected Marcaine directly into the peritoneal cavity
Measure Participants	20	20	20	20
Mean (Full Range) [Hours needed for safe mobilization]	6.7	6.5	3	6.4

4. Secondary Outcome

Title	Postoperative Morphine Use
Description	The reduction in cost comes from reducing the use of opioid which requires nursing supervision and also special pump to be delivered as in the cases of patient controlled analgesia. With that reduction, there will be a reduction in opioid related adverse events that mandate medical or nursing attention and prolong hospitalization, these adverse events include nausea and vomiting, delay mobilization due to drowsiness and alter mental status caused by opioid usage. For these reasons we are collecting data related to these adverse events
Time Frame	24 Hoiurs

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	IP Aerosolized Normal Saline	Nebulised Bupivacaine Intraperitoneally	Injected Bupivacaine Intraperitoneally
Arm/Group Description	No intraperitoneal therapeutics (No nebulised Bupivacaine) No Intraperitoneal Therapeutics: No Intraperitoneal Therapeutics given	Intraperitoneal nebulised 10mls. Normal Saline (No nebulised Bupivacaine) Normal Saline: Nebulised Normal Saline	Intraperitoneal Nebulised 10mls. Bupivacaione (Marcaine) Nebulised Bupivacaine intraperitoneally: Nebulised Marcaine (Bupivacaine)	Intraperitoeal Injected 10 mls.Bupivacaine (Marcaine) (No nebulised Bupivacaine) Injected Bupivacaine intraperitoneally: Injected Marcaine directly into the peritoneal cavity
Measure Participants	20	20	20	20
Mean (Full Range) [mg]	25.9	26.3	1	16.7

Adverse Events

Time Frame	24 Hours
Adverse Event Reporting Description	Nausea and Vomiting
Arm/Group Title	Control		IP Aerosolized Normal Saline		Nebulised Bupivacaine Intraperitoneally		Injected Bupivacaine Intraperitoneally
Arm/Group Description	No intraperitoneal therapeutics (No nebulised Bupivacaine) No Intraperitoneal Therapeutics: No Intraperitoneal Therapeutics given		Intraperitoneal nebulised 10mls. Normal Saline (No nebulised Bupivacaine) Normal Saline: Nebulised Normal Saline		Intraperitoneal Nebulised 10mls. Bupivacaione (Marcaine) Nebulised Bupivacaine intraperitoneally: Nebulised Marcaine (Bupivacaine)		Intraperitoeal Injected 10 mls.Bupivacaine (Marcaine) (No nebulised Bupivacaine) Injected Bupivacaine intraperitoneally: Injected Marcaine directly into the peritoneal cavity
All Cause Mortality
	Control		IP Aerosolized Normal Saline		Nebulised Bupivacaine Intraperitoneally		Injected Bupivacaine Intraperitoneally
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Control		IP Aerosolized Normal Saline		Nebulised Bupivacaine Intraperitoneally		Injected Bupivacaine Intraperitoneally
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Control		IP Aerosolized Normal Saline		Nebulised Bupivacaine Intraperitoneally		Injected Bupivacaine Intraperitoneally
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/20 (25%)		5/20 (25%)		1/20 (5%)		5/20 (25%)
Gastrointestinal disorders
Nausea and Vomiting	5/20 (25%)	9	5/20 (25%)	8	1/20 (5%)	4	5/20 (25%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.