Integrated Pulmonary Index and Opioid Based Patient Controlled Analgesia

Effective and Safe Morphine Dose for Patient Controlled Anesthesia in Supratentorial Craniotomies

An optimal analgesic therapy is very important for postoperative recovery. In recent years, several studies showed that the prevalence of the moderate to severe pain after craniotomy ranged from 69 to 87% of patients. The investigators showed that the use of morphine based patient controlled analgesia prevented moderate to severe postoperative pain in patients undergoing supratentorial craniotomy. Morphine related side effects such as sedation, miosis, respiratory depression, nausea and vomiting produce a general reluctance for their use in neurosurgery. Therefore, all patients were closely observed to detect opioid related side effects in the intensive care unit for 24 hours following surgery in our previous study. The Integrated Pulmonary Index (IPI) is a new tool that calculates respiratory and hemodynamic parameters noninvasively. In the present study the investigators will use different doses of morphine based patient-controlled analgesia and the IPI system to determine more effective and safer morphine dose for postoperative analgesia following supratentorial craniotomy.

Study Overview

• Status: Completed
• Conditions: Brain Tumors
• Intervention / Treatment: Drug: Morphine PCA 1 mg; Drug: Morphine PCA 0,5 mg; Drug: Placebo

Detailed Description

An optimal analgesic therapy is very important for postoperative recovery. In recent years, several studies showed that the prevalence of the moderate to severe pain after craniotomy ranged from 69 to 87% of patients. In our previous study, the investigators showed that the use of morphine based patient controlled analgesia prevented moderate to severe postoperative pain in patients undergoing supratentorial craniotomy. Morphine related side effects such as sedation, miosis, respiratory depression, nausea and vomiting produce a general reluctance for their use in neurosurgery. Therefore, all patients were closely observed to detect opioid related side effects in the intensive care unit for 24 hours following surgery in our previous study. The Integrated Pulmonary Index (IPI) is a new tool that calculates respiratory and hemodynamic parameters noninvasively. In the present study The investigators will use different doses of morphine based patient-controlled analgesia and the IPI system to determine more effective and safer morphine dose for postoperative analgesia following supratentorial craniotomy.

90 patients will randomize in 3 groups following supratentorial craniotomy. All patients will previously instruct on the patient-controlled analgesia pumps (Abbott Provider, Chicago, USA) and visual analogue scale (VAS) from 0 to 10, with 0 being no pain and 10 being the worst pain imaginable. All patients will use patient-controlled analgesia pumps for 24 hours following supratentorial craniotomy. In the Group 1 the patient-controlled analgesia pump will set to administer a bolus dose of 1 mg morphine on demand with a lockout period of 10 minutes and maximum 20 mg for 4 hours. In the Group 2 the patient-controlled analgesia pump will set to administer a bolus dose of 0.5 mg morphine on demand with a lockout period of 10 minutes and maximum 20 mg for 4 hours. In the Group 3 the patient-controlled analgesia pump will contain placebo. The Group 3 will take 50 mg dexketoprofen in the recovery room. Intra venous injections of dexketoprofen will repeat every 8 hours. If the VAS score will more than 4 the Group 3 patients will take 1 g paracetamol every 6 hours.

All patients will be observed by the Integrated Pulmonary Index (IPI). It is a new device that provides to recognise in a patients respiratory status. This software tool is a single index value ranging from 1 to 10 based on 4 physiological parameters: end tidal carbon dioxide, respiratory rate, oxygen saturation, pulse rate. Patients will asses at 10th minute, 1, 2, 6, 12, and 24 hours postoperatively. Sedation will evaluate according to Ramsay score 20. VAS scores, total morphine consumption, Ramsay score, blood pressure, heart rate and respiratory rate, the IPI score will record at each time pain will evaluate. Postoperative side effects, including rash, pruritus, nausea and vomiting will record at the same intervals and defined by a scale with 0 = absent or 1 = present. Moreover the lowest IPI score, the apnea count (longer than 30 seconds) and the count of the desaturation events will record in the postoperative 24 hours.

The 3 Groups will compare with respect to VAS scores, morphine consumption, IPI scores, the apnea count, the desaturation events and morphine related side effects during the 24 hours following supratentorial craniotomy.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34304
    • İstanbul University Cerrahpaşa Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 68 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: , brain tumors, elective supratentorial craniotomies,

• Conscious patients
• Elective supratentorial craniotomies
• ASA I-III

Exclusion Criteria:

• Unconscious postoperatively
• Chronic pain
• Opioid, dexketoprofen or paracetamol allergy
• Delirium
• Renal insufficiency
• Alcohol, opioid dependency
• Transsphenoidal pituitary surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morphine PCA 1 mg; The patient controlled analgesia device give 1mg morphine for each demand of the patient.	Drug: Morphine PCA 1 mg; PCA will set to administer a bolus dose of 1 mg morphine on demand with a lockout period of 10 minutes and maximum 20 mg for 4 hours.; Other Names: Morphine sulphate 1 mg
Active Comparator: Morphine PCA 0,5 mg; The patient controlled analgesia device give 0,5 mg morphine for each demand of the patient.	Drug: Morphine PCA 0,5 mg; PCA set to administer a bolus dose of 0.5 mg morphine on demand with a lockout period of 10 minutes and maximum 20 mg for 4 hours.; Other Names: Morphine sulphate 0,5 mg
Placebo Comparator: Placebo; The patient controlled analgesia device give 2 mL serum physiologic for each demand of the patient.The Group 3 will take 50 mg dexketoprofen in the recovery room. Intra venous injections of dexketoprofen will repeat every 8 hours. If the VAS skore more than 4 the Group 3 patients will take 1 g paracetamol every 6 hours.	Drug: Placebo; the PCA will contain placebo; Other Names: serum physiologic, dexketoprofen trometamol, paracetamol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Integrated pulmonary index system	Integrated pulmonary index system will be used to determine more effective and safer morphine dose for postoperative analgesia following supratentorial craniotomy. This software tool is a single index value ranging from 1 to 10 based on 4 physiological parameters: end tidal carbon dioxide, respiratory rate, oxygen saturation, pulse rate.	24 hour postoperatively

Collaborators and Investigators

• Sponsor: Istanbul University
• Investigators: Study Director: Yusuf Tunali, Professor, Cerrahpasa Medical School

Publications and helpful links

General Publications

• Gottschalk A, Berkow LC, Stevens RD, Mirski M, Thompson RE, White ED, Weingart JD, Long DM, Yaster M. Prospective evaluation of pain and analgesic use following major elective intracranial surgery. J Neurosurg. 2007 Feb;106(2):210-6. doi: 10.3171/jns.2007.106.2.210.
• Thibault M, Girard F, Moumdjian R, Chouinard P, Boudreault D, Ruel M. Craniotomy site influences postoperative pain following neurosurgical procedures: a retrospective study. Can J Anaesth. 2007 Jul;54(7):544-8. doi: 10.1007/BF03022318.
• Mordhorst C, Latz B, Kerz T, Wisser G, Schmidt A, Schneider A, Jahn-Eimermacher A, Werner C, Engelhard K. Prospective assessment of postoperative pain after craniotomy. J Neurosurg Anesthesiol. 2010 Jul;22(3):202-6. doi: 10.1097/ANA.0b013e3181df0600.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: February 28, 2018
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Integrated pulmonary index, opioid side effects
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Analgesics, Opioid; Narcotics; Morphine; Dexketoprofen trometamol
• Other Study ID Numbers: Cerrahpasa Neuroanaesthesia

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No