Authors:
1Mansoor Soltanzadeh : Associate Professor of Anesthesiology, Department of
Anesthesiology of Imam Khomeini Hospital, Ahwaz Jundishapur University of Medical sciences, Iran
2Fatemeh Javaherforoosh : Assistant Professor of Anesthesiology, Department of
Anesthesiology of Imam Khomeini Hospital, Ahwaz Jundishapur University of Medical sciences, Iran
3Leila Azinfar: Assistant of Anesthesiology, Department of Anesthesiology of Imam
Khomeini Hospital, Ahwaz Jundishapur University of medical sciences, Iran
4Banafsheh Valian Boroojeni: Assistant of Anesthesiology, Department of
Anesthesiology of Imam Khomeini Hospital, Ahwaz Jundishapur University of medical sciences, Iran
Corresponding author: Mansoor Soltanzadeh: Associate Professor of Anesthesiology,
Department of Anesthesiology of Imam Khomeini Hospital, Ahwaz Jundishapur University of
Medical sciences, Iran- Tel:0098-611-3743050
1

Abstract:
Background: One of the side effects of post-operative opioids drugs administration in the patients on ventilator devises is prolongation of ventilation with ventilator. In this study we used of infusion of the paracetamol and investigated its' effects on duration of ventilation for these patients on the ventilator.
Methods: In a double-blind clinical trial, 40 patients selected for abdominal and pelvic surgery, were studied in two groups of 20 patients. After operation, two groups received ventilator therapy. In the case group, patients received infusion of 1 gr paracetamol in 100cc normal saline and in the control group patients received placebo. The duration of ventilator therapy in the two groups recorded.
Results: The mean duration of ventilator therapy was 64.3±40.6 minutes in case group and
204.5±112.7 minutes in the control group (P˂0.01).
Conclusion: The mean duration of ventilator therapy in the case group was significantly shorter than the control group.
Keywords: Cyclooxygenase – Large surgery – Opioid – Paracetamol – Ventilator
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Introduction:
Large abdominal and thoracic surgeries have with increase of airway resistance, decrease of lung compliance and decrease of lung capacities and volumes. After the upper abdominal surgery and also thoracic surgery, Lung compliance, tidal volume and vital capacity will decrease to
33%, 20% and 25-50% respectively.
Furthermore, after lower abdominal surgery, expiratory reservoir volume decreases to 25% and in upper abdominal surgery and thoracic surgery decreases to 60%
1-6
.
Functional residual capacity is the most important factor between pulmonary volumes and capacities; in which; due to several reasons such as closure of small airways, decreased muscle strength duo to pain, changes in movement of diaphragm, decreased diaphragm and lung compliance and increased abdominal pressure following supine position, causes a majority of pulmonary complications after large surgeries 7-9 . Some patients may require respiratory protection using mechanical ventilation system after the operation due to the stated factors.
Several drugs and methods are suggested to decrease pain after the operation
10
. Patients with endotracheal tube who are transported to ICU from the operation room suffer some problems in which the most important are pain, endotracheal tube intolerance and restlessness
11
. For analgesia and sedation of patients in the ICU and also toleration of endotracheal tube, several drugs are used that the most commonly used ones are opium. Although using the opioid drugs has its own advantages, they can come with complications and side effects for the patient.
Opioids have many side effects in which suppression of breathing, sleeping, and gastrointestinal complications (such as ileus, nausea, vomiting and constipation), urinary retention and pruritus are mentionable
12
. Another one of Opium side effects is drowsiness in patient that may need the patient ventilator support for a longer period and as result, increases the complications caused by endotracheal tube and ventilator. Prolonged ventilation with ventilator may increase incidence of respiratory tract infection, atelectasis, barrow trauma, cardiovascular complication, tracheal stenosis and respiratory muscles weakness
13
. Other methods that simultaneously reduces the need for narcotic analgesia, such as a local anesthetics, neuroaxial block and use of non-steroidal anti-inflammatory drugs has long been considered; but using each one of them has its own complications
14
.
Paracetamol is a cyclooxygenase (COX) II inhibitor; which has a central effect on the serotonergic system. Intravenous paracetamol with a maximum dose of 4 𝑔𝑟/𝑑𝑎𝑦 does not have the complications of non-steroidal anti-inflammatory and opioid drugs
15
. Unlike non-steroidal anti-inflammatory drugs, paracetamol is a weak anti-inflammatory drug without the side effects of COX stimulation such as renal, gastrointestinal and platelet dysfunction. It has a very few number of drug interactions and administering it during pregnancy and breastfeeding is not banned
16, 17
. The goal of this research is study of intravascular effects of paracetamol on duration of mechanical ventilation in the patients after large surgeries.
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Material and Methods:
After approval by ethics committee of the university and consenting the patients before anesthesia, 40 patients, whom were randomized in a double-blind study, candidated for abdominal or pelvic surgery which seemed to require mechanical ventilation and analgesia after the surgery ,were chose. Elective surgery includes Gastrostomy, hemi colectomy, total colectomy, resection - anastomosis of the small intestine and Whipple. Patients were adults aged more than 18 to 69 years, selected based on ASA physical status class II and III. Exclusion criteria included any known allergies or sensitivities or contraindications to drugs or paracetamol, impaired liver function (transaminase twice normal), impaired renal function, smoking, or any lung disease prior abuse alcohol - drugs and medication, pregnant and lactating women. Patients in the operating room went under general anesthesia with same drugs. Induction of anesthesia on patients was administered using midazolam 0.05mg/Kg, fentanyl 2μgr/Kg, sodium thiopental 3 mg/Kg and Atracurium 0.5 mg/Kg was used. The only opioid drug used during surgery was fentanyl. Also fentanyl 1.5µgr/Kg was administered for analgesia during surgery and before getting skin stitched. Intubated patients were transferred directly from the operating room to the intensive care unit and were connected to the ventilator. Patients were randomized in two groups during transferring to the ICU. The first group received intravenous paracetamol 1 gr in 100 cc saline solution every 6 hours for 24 hours immediately after entering the intensive care unit and the second group received placebo (saline ¬ 100 cc). Duration of ventilator support was recorded for all patients on the ventilator. Furthermore, for pain management of patients in the ICU fentanyl with a dose of 1µ/kg was administered by using behavioral pain scales (BPS)
18
, and the amount of used fentanyl and BPS was recorded in hours
0 (upon arrival to ICU),1, 2, 4, 6, 12 and 24. BPS was calculated based on three factors; face gestures (scaled 1 to 4), limb movement (scaled 1 to 4) and tolerating the mechanical ventilation system (scaled 1 to 4) (6). Minimum BPS score was 3 and maximum was 12 and if the total score was more than 4, opium was administered. Data gathered from patients was analyzed using
SPSS 17 software application. Chi square, fisher’s exact test and T-Test statistical test were performed to compare the data between the groups; and if P-value was less than 0.05, difference was known as significant.
Results and Discussion:
The mean age was 55.75±10.08 years in the study group and 58.35±8.89 years in the control group. Difference of age in study and control group was not statistically significant (p=0.372)
(diagram 1).
The frequency of sex was 7 women (35%) and 13 men (65%) in the control group and 10 women (50%) and 10 men (50%) in the study group and no significant statistical difference between two groups (p=0.593). The mean weight was 68.9±4.52 kg in the control group and
69.2±5.02kg in the study group. Difference of weight in study and control group was not statistically significant (p=0.867) (diagram 2). The mean patient’s duration on the ventilator in
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the ICU in the study group was 64.3±40.6 minutes and 204.5±112.7 minutes in the control group which had a significant difference (P=0.001).
Although there was no significant difference between the pain in patients in both groups upon arrival, severity of pain had a significant difference between two groups during the 1 st
, 2 nd
, 4 th
,
6 th
, 12 th
and 24 th
hours (P=0.001) (diagram 3).
The rate of opium consumption in both case and control groups, the mean rate of opium consumption in 24 hours was 64.5±2.56 µg in the cntrol group and 61.9±4.330 µg in the study group and a significant difference was observed between two groups (p=0.001).
Based on the achieved results in this study, the mean duration of ventilator therapy in the group which received intravenous paracetamol (64.3±40.6 minutes) was significantly less than the control group (204.5±112.7 minutes) (P<0.01).
A similar research was performed by Memis and his colleagues (in 2010) based upon intravenous effects of paracetamol in reducing the time required for extubation in 40 patients.
The results of that study also showed decrease of duration of patient’s need of ventilation in the control group. In that study intravenous paracetamol not only reduced the dose of administered opium and extubation time, but it also decreased the opium side effects such as vomiting, nausea and pruritus
19
.
For analyzing the cases of decrease of ventilator therapy duration in intravenous paracetamol received patients, paracetamol’s pharmacological characteristics must be considered.
By inhibiting cyclooxygenase-2 isoenzyme and cooxygenase 3 (COX3) in the central nervous system and inhibiting cooxygenase 1 (COX1) isoenzyme in peripheral tissues, Intravenous
Paracetamol is considered as a non-opioid analgesic used to treat mild and moderate pain and can be mixed by opium in order to reduce the required dose in severe pain 15 . Unlike opioids, paracetamol lacks the effects of sedation and respiratory depression and it can used with opioid drugs to reduce the required dose of opioids and thus decreasing sedation and respiratory depression in the patients.
In our study, Because the patients in the case group receiving paracetamol in the first 24 hours after the surgery in the ICU, the severity of patient’s pain and thus their need for fentanyl was significantly decreased. Due to decreasing the dose of opium, patients in the case group had less sedation and respiratory depressions in comparison to the control group and as result reduce the time required for ventilate patients with ventilator.
Conclusion:
The mean duration of ventilator therapy in the case group was significantly shorter than the control group.
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Acknowledgement:
It is necessary to gratitude from the personnel of operating room and ICU who helped us in this research.
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90 diagram2: comparison of weight in case and control group
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Diagram 3: BPS in case and control groups
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