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Table of Contents
ORIGINAL ARTICLE
Year : 2016  |  Volume : 32  |  Issue : 2  |  Page : 210-213

Efficacy of intravenous paracetamol on pressor response in patients undergoing cesarean section under general anesthesia


Department of Anaesthesia, Aga Khan Hospital, Karachi, Pakistan

Date of Web Publication10-May-2016

Correspondence Address:
Sanum Kashif
House No. 6A, Unique Road, Rawalpindi, 46000
Pakistan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9185.173332

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  Abstract 

Background and Aims: Profound hemodynamic alterations due to stress and pain during endotracheal intubation may cause deleterious effects. The purpose of this study was to evaluate the effect of intravenous (IV) paracetamol on hemodynamic changes due to endotracheal intubation during cesarean section under general anesthesia.
Material and Methods: Random allocation of one hundred and ten patients in two groups (Group A - placebo and Group B - paracetamol), was achieved as per computer generated table. The placebo (normal saline) and paracetamol solutions looked identical as both were available in 100 ml piggy bags and were labeled as study drug. Infusion of the drug was given 1 h before surgery. Two baseline readings of heart rate, systolic blood pressure (BP), diastolic BP and mean BP were recorded before induction, and these readings were repeated during intubation. Detrimental effect on neonate was evaluated by Apgar score measured at 1 and 5 min after birth.
Results: There were no significant demographic differences found between the two groups. Hemodyamic changes during intubation also did not differ between the two groups.
Conclusion: Administration of IV paracetamol 1 h before cesarean section has no significant effect in preventing hemodynamic changes at the time of endotracheal intubation.

Keywords: Cesarean section, endotracheal intubation, hemodynamic changes


How to cite this article:
Kashif S, Hamid M. Efficacy of intravenous paracetamol on pressor response in patients undergoing cesarean section under general anesthesia. J Anaesthesiol Clin Pharmacol 2016;32:210-3

How to cite this URL:
Kashif S, Hamid M. Efficacy of intravenous paracetamol on pressor response in patients undergoing cesarean section under general anesthesia. J Anaesthesiol Clin Pharmacol [serial online] 2016 [cited 2021 May 7];32:210-3. Available from: https://www.joacp.org/text.asp?2016/32/2/210/173332


  Introduction Top


During general anesthesia (GA), endotracheal intubation (ETI) results in stimulation of sympathetic nervous system and catecholamine release, and therefore, increase in BP and heart rate (HR). [1] The ETI-induced catecholamine release can result in fatal arrhythmia and intracranial hemorrhage. [2] Opioids have been used to minimize these responses to short-term stimuli such as ETI. However, opioid administration is not recommended in GA in parturients for cesarean section, because of its depressant effects on the newborn.

Hemodynamic alterations due to stress and pain as a result of ETI may decrease uteroplacental blood flow and lead to adverse neonatal outcomes. [3] Many drugs have been employed to blunt the ETI response like lignocaine and opioid, nonnarcotic analgesics and gabapentin. Paracetamol has a well-established safety and analgesic profile [4] and is a safe drug during pregnancy. The main mechanism of action is inhibition of cyclo-oxygenase enzyme which is responsible for the production of prostaglandins, an important mediator of inflammation, pain and fever. Its maximum recommended dose in adults is 4000 mg/day. Onset of action is within 5-10 min of administration. The peak analgesic effect is obtained in 1 h and the duration of action is 4-6 h. [5],[6] The purpose of the study was to observe the efficacy of intravenous paracetamol in preventing hemodynamic changes due to pain in cesarean sections at intubation, as well as its effect on neonatal Apgar score. [7],[8]


  Material and Methods Top


This study was conducted after obtaining the institutional ethical review committee approval and an informed patient consent. The study did not include American Society of Anesthesiologists-III and above patients, emergency surgeries, patients allergic to paracetamol, anticipated difficult intubation with mallampatti Grade-III and above, preeclampsia and eclampsia. Patients with known hypertension, peripheral vascular disease, ischemic heart disease, cardiac arrhythmias or having cardiac pacemaker, patients taking any HR modifying drugs, monoamine-oxidase inhibitors, or any drug affecting autonomic nervous system were also excluded. Random allocation of patients in two groups was done by the hospital pharmacy as per computer generated table. Patients were allocated to one of the two study groups. The placebo group (n = 55) received normal saline and paracetamol group (n = 55) received 1 g intravenous paracetamol. The placebo or paracetamol solutions were given to the patient in a 100 ml piggy bag which was labeled as study drug. The drug was given 1 h before the surgery by a registered ward nurse who was not involved in the OR management of the patient. Every patient was given aspiration prophylaxis 1 h before going to the operating room. In the operating room, patient was placed in a supine position with 15° left tilt. Two intravenous lines were placed. Ringers lactate was given at the rate of 200 ml/h to all patients as soon as a patient entered the OR. Two baseline readings of HR, systolic BP (SBP), diastolic BP (DBP) and mean BP (MBP) were recorded before induction. General anesthesia was induced with rapid sequence induction by using the calculated dose of propofol (2 mg/kg) and succinylcholine (1.5 mg/kg). Macintosh laryngoscope blade size three with an endotracheal tube of size 7.0 mm internal diameter was inserted. O 2 /N 2 O 50% and 1% isoflurane were used. EtCO 2 was kept 30-35 mmHg throughout the procedure. Final HR, SBP, DBP and MAP readings were taken as soon as intubation started. Datex Ohmeda S/5 monitor was used to record HR and BP. Pethidine (1 mg/kg), atracurium (0.5 mg/kg) and syntocinon 40 units (10 units stat and 30 units in 500 ml fluid at 100 ml/h) were given after the cord was clamped. Hypotension (BP <20% of baseline) was treated by giving IV fluid boluses (3 × 2 ml/kg). Metoprolol 2 mg was available in case of hypertension. All variables (HR, SBP, DBP and MAP) and their management were noted in data collection sheets at baseline and the final outcome was measured at intubation. To see any detrimental effect on neonate, all neonates were assessed and Apgar score was measured at 1 and 5 min after the birth.

Statistical analysis

All statistical analysis was performed using Statistical Packages for Social Science version 19 (SPSS Inc., Chicago, IL, USA). Data were expressed as mean (standard deviation) for quantitative variables like age, weight, SBP, DBP, HR. Independent sample t-test and Mann-Whitney tests were applied to compare the mean/median difference between groups for age, weight. The paired t-test was used to compare within-subject effect for HR and BP. P < 0.05 was considered as significant.


  Results Top


Mean age and weight were not significantly different between the groups [Table 1].
Table 1: Comparison of demographic variables between groups

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Comparison of mean HR, DBP, SBP and MAP at baseline and at intubation is presented in [Table 2]. Average HR, SBP, DBP and MAP were increased significantly from baseline in both groups, but significant differences were not observed in inter-group comparison as shown in [Table 2].
Table 2: Comparison of mean hemodynamic parameters between groups

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Mean percent increase in HR, SBP, DBP and MAP from baseline were not significantly different in the two groups [Figure 1].
Figure 1: comparison of mean percent change of hemodynamic parameters between groups. Group A: Normal Saline; Group B: Paracetamol

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There was no significant difference between groups in altering hemodynamic during intubation when the age was divided into 30 or less and more than 30 years (P = 0.57).

Apgar score at 1 and 5 min remained above 7 in both the groups.


  Discussion Top


Hemodynamic stability at intubation is important in all surgeries, under GA especially in cesarean sections where two lives are involved. Profound hemodynamic alterations due to stress and pain during intubation may cause deleterious effects. It may decrease uteroplacental blood flow and lead to adverse neonatal outcomes. [9] There are many published controlled trials for the pharmacological modifications of the sympathetic response to laryngoscopy, tracheal intubation, and surgical stimulation, including opioids, tenoxicam, ketorolac, lidocaine, and paracetamol. [10] However, opioids can readily cross the placenta and lead to adverse neonatal outcomes such as serious respiratory depression and bradycardia if given before clamping. [11] Nonsteroidal antiinflammatory drugs also cannot be used due to their effect on maternal and fetal hemorrhage and premature closure of fetal ductus arteriosus. [12],[13]

Paracetamol is a safe drug during all stages of pregnancy and labor. [14] It belongs to aniline analgesic class of drugs and is an active metabolite of phenacetin. Its chemical name is para-acetylaminophenol. It has a well-established safety and analgesic profile. The main mechanism of action is inhibition of cyclo-oxygenase enzyme, which is responsible for the production of prostaglandins, an important mediator of inflammation and pain. Onset of action is within 5-10 min after the start of administration. Oral paracetamol is widely used as an over-the-counter nonopioid analgesic and antipyretic with few contraindications and lack significant drug interactions. [15]

Park et al. in his study compared the effects of remifentanil at 0.5 or 1.0 μg/kg on maternal hemodynamic responses to laryngoscopy and tracheal intubation in pregnant patients undergoing cesarean delivery under general anesthesia. SBP was increased by tracheal intubation in both groups. The peak systolic arterial pressure after intubation was greater in the R0.5 group than in the R1.0 group, whereas it did not exceed baseline values in either group. HR increased significantly above baseline in both groups with no significant differences between the groups. Neonatal Apgar scores and umbilical arterial and venous pH and blood gas values were comparable between the groups. [16] A double-blind randomized placebo-controlled study showed less mean HR change in the paracetamol group when compared to control group (76.1 ± 13.1 (95% confidence interval (CI): 69.9-82.23) vs. 80.6 ± 15 (95% CI: 73.6-87.62)). [17]

Another randomized controlled trial showed that intraoperative hemodynamics in cesarean sections were not statistically significant between clonidine versus control groups (9.1% vs. 12.7% respectively; P > 0.05). [18] The rationale of this study was to observe the efficacy of intravenous paracetamol in preventing hemodynamic changes due to pain in cesarean sections at intubation as well as its effect on neonatal Apgar score. As the literature shows that paracetamol has been used safely in labor as well as before induction to observe its analgesic effects postoperatively. Therefore, this study was designed to evaluate the efficacy of intravenous paracetamol in the prevention of hemodynamic changes due to pain on ETI. Significant difference was not observed between the groups. None of the patients in any intervention group had any untoward effects related to paracetamol. [19]

Although paracetamol proves to be a safe drug for both mother and neonate, but it probably has no role in preventing hemodynamic alterations due to intubation. Its combination with other nonnarcotic analgesics may be an area, which needs further research.


  Conclusion Top


Administration of intravenous paracetamol 1 h before cesarean section has no significant effect in preventing hemodynamic changes at the time of ETI. There were no immediate side-effects of paracetamol on patient or neonate in both the groups.

 
  References Top

1.
Van den berg AA, Ayem H, Soomro A, Rasheed A, Baloch M. Reducing cardiovascular responses to laryngoscopy and tracheal intubation: A comparison of equipotent doses of tramadol, nalbuphine and pethidine, with placebo. Middle East J Anesthesiol 2004;17:1023-36.  Back to cited text no. 1
    
2.
Coskun D, Mahli A, Yilmaz Z, Cizmeci P. Anesthetic management of caesarean section of a pregnant woman with cerebral arteriovenous malformation: A case report. Cases J 2008;1:327.  Back to cited text no. 2
    
3.
Park BY, Jeong CW, Jang EA, Kim SJ, Jeong ST, Shin MH, et al. Dose-related attenuation of cardiovascular responses to tracheal intubation by intravenous remifentanil bolus in severe pre-eclamptic patients undergoing Caesarean delivery. Br J Anaesth 2011;106:82-7.  Back to cited text no. 3
    
4.
Lesko SM, Mitchell AA. The safety of acetaminophen and ibuprofen among children younger than two years old. Pediatrics 1999;104:e39.  Back to cited text no. 4
    
5.
Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J 2008;22:383-90.  Back to cited text no. 5
    
6.
Bannwarth BL, Pehourcq F. Pharmacological rationale for the clinical use of paracetamol; pharmakinetic and pharmadynamic issues. Drugs 2003;63:2-5.  Back to cited text no. 6
    
7.
Jouppila P, Kuikka J, Jouppila R, Hollmén A. Effect of induction of general anesthesia for cesarean section on intervillous blood flow. Acta Obstet Gynecol Scand 1979;58:249-53.  Back to cited text no. 7
    
8.
Palmer GM, Atkins M, Anderson BJ, Smith KR, Culnane TJ, McNally CM, et al. I.V. acetaminophen pharmacokinetics in neonates after multiple doses. Br J Anaesth 2008;101:523-30.  Back to cited text no. 8
    
9.
Casey BM, McIntire DD, Leveno KJ. The continuing value of the Apgar score for the assessment of newborn infants. N Engl J Med 2001;344:467-71.  Back to cited text no. 9
    
10.
Inal MT, Celık NS, Tuncay FS. Paracetamol infusion is better I.V. Than I.V. Meperidine infusion for postoperative analgesia after caesarean section. Internet J Anesthesiol 2007;15:1092-406.  Back to cited text no. 10
    
11.
Alhashemi JA, Alotaibi QA, Mashaat MS, Kaid TM, Mujallid RH, Kaki AM. Intravenous acetaminophen vs oral ibuprofen in combination with morphine PCIA after Cesarean delivery. Can J Anaesth 2006;53:1200-6.  Back to cited text no. 11
    
12.
Gin T, Kan AF, Lam KK, O'Meara ME. Analgesia after caesarean section with intramuscular ketorolac or pethidine. Anaesth Intensive Care 1993;21:420-3.  Back to cited text no. 12
    
13.
Hyllested M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: A qualitative review. Br J Anaesth 2002;88:199-214.  Back to cited text no. 13
    
14.
Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S. Paracetamol: New vistas of an old drug. CNS Drug Rev 2006;12:250-75.  Back to cited text no. 14
    
15.
Elbohoty AE, Abd-Elrazek H, Abd-El-Gawad M, Salama F, El-Shorbagy M, Abd-El-Maeboud KH. Intravenous infusion of paracetamol versus intravenous pethidine as an intrapartum analgesic in the first stage of labor. Int J Gynaecol Obstet 2012;118:7-10.  Back to cited text no. 15
    
16.
Grundmann U, Wörnle C, Biedler A, Kreuer S, Wrobel M, Wilhelm W. The efficacy of the non-opioid analgesics parecoxib, paracetamol and metamizol for postoperative pain relief after lumbar microdiscectomy. Anesth Analg 2006;103:217-22.  Back to cited text no. 16
    
17.
Ebneshahidi A, Mohseni M. Premedication with oral clonidine decreases intraoperative bleeding and provides hemodynamic stability in cesarean surgery section. Anesth Pain 2011;1:30-6.  Back to cited text no. 17
    
18.
Wilson-Smith EM, Morton NS. Survey of IV. Paracetamol (acetaminophen) use in neonates and infants under 1 year of age by UK anesthetists. Paediatr Anaesth 2009;19:329-37.  Back to cited text no. 18
    
19.
Isbister G, Whyte I, Dawson A. Pediatric acetaminophen overdose. J Toxicol Clin Toxicol 2001;39:169-72.  Back to cited text no. 19
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  [Table 1], [Table 2]


This article has been cited by
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[Pubmed] | [DOI]



 

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