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ORIGINAL ARTICLE
Year : 2013  |  Volume : 7  |  Issue : 3  |  Page : 331-335  

A comparative study of the efficacy of intravenous Paracetamol and Dexmedetomidine on peri-operative hemodynamics and post-operative analgesia for patients undergoing laparoscopic cholecystectomy


Department of Anesthesiology and Critical Care, Bankura Sammilani Medical College and Hospital, Bankura, West Bengal, India

Date of Web Publication18-Dec-2013

Correspondence Address:
Sarbari Swaika
Department of Anesthesiology and Critical Care, Bankura Sammilani Medical College and Hospital, Bankura - 722 102, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0259-1162.123225

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   Abstract 

Background: Unrelieved post-operative pain may result in the physical suffering as well as multiple physiological and the psychological consequences, which may adversely affect the peri-operative outcome and contribute to increase the length of stay in hospital.
Objectives: We designed this study to evaluate the effect of IV Paracetamol and Dexmedetomidine as multimodal analgesic technique on post-operative analgesia and to reduce the consumption of the systemic opioid and its adverse effects in cases of laparoscopic cholecystectomy.
Materials and Methods: Eighty consenting, American society of Anesthesiologist-physical status-I (ASA-PS-I), female patients, aged 19-60 year was randomly assigned to one of the following two groups: Group P (n = 40) received IV 1 g Paracetamol infusion over 10 min pre-operatively and 6 hourly thereafter and Group D (n = 40) received IV Dexmedetomidine 1 ΅g/kg bolus over 10 min pre-operatively and 0.2-0.4 ΅g/kg/h thereafter for 24 h. Peri-operative hemodynamic variables, post-operative pain scores, and the need for rescue analgesics were recorded and compared.
Results: Profiles of intra-operative hemodynamic changes were similar in both groups in respect to heart rate (HR), diastolic blood pressure, mean arterial pressure except in the systolic blood pressure where Dexmedetomidine significantly reduced it in compare to Paracetamol (P = 0.014). Post-operatively 4 th h and 24 th h changes in mean HR between two groups was a statistically significant (P < 0.05). Visual analog scale scores were significantly lower in the Group P compared with Group D at 8 th , 16 th , and 24 th h (P < 0.001). Sedation score were statistically higher in the Group D compared with the Group P at post-operative 4 th , 8 th , 16 th , and 24 th h (P < 0.006).
Conclusion: Adjunctive use of both Paracetamol and Dexmedetomidine infusion reduced opioid use. However, Paracetamol peri-operatively provides adequate analgesia with the less sedation whereas Dexmedetomidine provides analgesia and co-operative sedation.

Keywords: Dexmedetomidine, laparoscopic cholecystectomy, multimodal analgesia, Paracetamol


How to cite this article:
Swaika S, Parta N, Chattopadhyay S, Bisui B, Banarjee SS, Chattarjee S. A comparative study of the efficacy of intravenous Paracetamol and Dexmedetomidine on peri-operative hemodynamics and post-operative analgesia for patients undergoing laparoscopic cholecystectomy. Anesth Essays Res 2013;7:331-5

How to cite this URL:
Swaika S, Parta N, Chattopadhyay S, Bisui B, Banarjee SS, Chattarjee S. A comparative study of the efficacy of intravenous Paracetamol and Dexmedetomidine on peri-operative hemodynamics and post-operative analgesia for patients undergoing laparoscopic cholecystectomy. Anesth Essays Res [serial online] 2013 [cited 2020 May 28];7:331-5. Available from: http://www.aeronline.org/text.asp?2013/7/3/331/123225


   Introduction Top


Peritoneal insufflation to intra-abdominal pressure >10 mmHg induces a significant alteration of hemodynamics. Catecholamines, renin-angiotensin system, and especially vasopressin are all released during the presence of pneumoperitoneum and may contribute to increase in the afterload. Use of α-2 adrenergic agonists such as clonidine or Dexmedetomidine significantly reduces hemodynamic changes and anesthetic requirements as it has sedative, analgesic, and anxiolytic properties. Dexmedetomidine has greater affinity to α-2 A subtype, which may account for superior analgesic versus clonidine, does not interact with the GABA mimetic system so does not depress respiratory drive and centrally mediated reduction in sympathetic tone offers cardio-protective effect. [1]

Though, the laparoscopy allows a significant reduction in post-operative pain, there may be pain resulting from the diaphragmatic irritation. Multimodal analgesia [2] is now recommended to prevent and treat the post-laparoscopic pain. [1] Paracetamol and Dexmedetomidine are both effective component in respect of multimodal analgesia in combination with opioids. Paracetamol has both analgesic and antipyretic effects similar to aspirin and it is devoid of many side-effects of NSAIDs such as GI ulceration, impaired platelet function, and adverse cardiorenal effects. [3] The mechanism of action is considered to be inhibition of putative central cycloxygenase (COX) 3 causing reduced production of prostaglandin in CNS. [4] In addition, there may be modulation of descending inhibitory serotonergic pathways and it may act on opioidergic system and NMDA receptors. [5]

Post-operative nausea and vomiting (PONV) is a distressing complaint in laparoscopic cholecystectomy, which is aggravated by use of opioids. The anesthetic and opioid sparing effects of Dexmedetomidine in the early post-operative period may decrease the risk of respiratory depression and incidence of PONV. [1]


   Materials and Methods Top


After obtaining institutional ethical clearance at and written informed consent, 80 female patients aged 19-60 year, ASA-PS-I scheduled for laparoscopic cholecystectomy were taken for these randomized study. Patients with body weight >80 kg, cardiovascular disease, broncho-pulmonary disease, renal, neurologic, gastrointestinal, and hepatic dysfunction, history of allergy, long-term use of medications such as beta-blocker and other anti-hypertensives, antipsychotic, analgesic, alcohol, sedative, TCA etc., patients with psychiatric illness, patient refusal were excluded from this study.

Patients were randomly assigned to one of the following two groups: Group P (n = 40) received IV 1 g Paracetamol infusion over 10 min pre-operatively and 6 hourly thereafter and Group D (n = 40) received IV Dexmedetomidine 1 μg/kg bolus over 10 min pre-operatively and 0.2-0.4 μg/kg/h thereafter for 24 h using a computer generated random-number table.

In the pre-operative holding area the patients learned and familiarized about 10 point visual analog scale (VAS) to assess their baseline pain with 0 = none to 10 = maximum. Immediately before entering the operating room patients were pre-medicated with the Midazolam 2 mg, Ondansetron 4 mg and Glycopyrrolate 0.2 mg IV. Intra-operative monitoring devices included pulse-oximetry, non-invasive blood pressure, ECG, and capnography.

After obtaining base line measurement of heart rate (HR), systolic blood pressure (SBP) diastolic blood pressure (DBP) and mean arterial pressure (MAP), infusion of Paracetamol 1 g was given over 10 min for Group P and infusion Dexmedetomidine was given 1 μg/kg (diluting in normal saline making a 50 ml solution) over 10 min and 0.2-0.4 μg/kg/h thereafter for 24 h for Group D. Anesthetic induction was accomplished with pre-oxygenation, injection Fentanyl 1 μg/kg, and injection Propofol 2 mg/kg IV followed by injection Succinylcholine 1.5 mg/ kg IV to facilitate tracheal intubation. Anesthesia was maintained with nitrous oxide (N 2 O) 66% and oxygen (O 2 ) 34% mixture in combination with 0.5-1 vol% Isoflurane, and injection Atracurium. The end tidal carbondioxide was maintained within 35-40 mmHg. The HR, SBP, DBP, and MAP were recorded intra-operatively at 5 min, 15 min, 30 min, 45 min, and 60 min starting from the completion of bolus dose infusion of study drug and HR and MAP post-operatively at 1 st , 4 th , 8 th , 16 th , and 24 th h. MAP were maintained within ± 25% of the baseline values by varying the inspired Isoflurane concentration. Hypotension [6] (defined as MAP value <25% of the baseline value on 2 consecutive readings within 2-3 min) not responding to reduction in inspired Isoflurane concentration and 200 ml fluid bolus was treated with injection Phenylephrine. The infusion of study medication was discontinued if the hypotension persisted >2 min after these interventions. Upon return of the MAP ± 25% of the baseline values the study medication infusion was resumed at 50% of the initial infusion rate. In the presence of hypertension [6] (defined as MAP value >25% of the baseline value on two consecutive readings within 2-3 min) and or tachycardia [6] (defined as HR value >25% of the baseline value on 2 consecutive readings within 2-3 min) inspired concentration of Isoflurane and study medication was increased. Bradycardia [6] (defined as HR <45/min) persisting for >2 min was treated with injection Atropine. Post-operative pain and sedation score were recorded at 1 st , 4 th , 8 th , 16 th , and 24 th h.

During the operation, patients received similar amounts of IV crystalloid solutions. Residual neuromuscular block was reversed with Neostigmine 40 μg/kg and Glycopyrrolate 5 μg/kg IV after the end of operation. Post-operatively injection Tramadol was given as rescue analgesic at a dose of 100 mg IV when VAS > 5.

Data were expressed as mean ± SD and the statistical analysis was performed using a standard software package. For continuous variables one-way analysis of variance (ANOVA) and repeated measures of ANOVA were used to evaluate the changes among the groups. Wilks' Lambda test was used to analyze the parametric data.


   Results Top


A total of 80 patients were enrolled and divided into two groups (n = 40). Two patients were excluded from final analysis due to repeated hypotension and bradycardia.

[Table 1] shows there were no significant differences among the two groups with respect to age, weight, and height (P > 0.05).
Table 1: Baseline demographic data

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Intra-operative hemodynamic parameters were recorded at 5, 15, 30, 45, and 60 min after the completion of bolus dose infusion of study medication. [Table 2] shows profiles of hemodynamic changes, which were similar in both groups in respect to HR, DBP, MAP except in SBP where Dexmedetomidine significantly reduced it in compare to Paracetamol (P = 0.014).
Table 2: Intra-operative hemodynamic parameters

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Post-operative hemodynamic parameters were recorded at 4 th , 8 th , 16 th , and 24 th h. No significant differences in the post-operative hemodynamic parameters were seen in MAP, as shown in [Table 3]. Mean HR ranges from (83 ± 3) to (93 ± 4) for the Group P whereas, it ranges between (74 ± 3) to (83 ± 3) in Group D. Post-operatively 4 th h and 24 th h changes in mean HR between two groups was statistically significant (P < 0.05).
Table 3: Post-operative hemodynamic parameters

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VAS score for post-operative pain were measured in a scale of 10 where 0 = no pain and 10 = maximum pain at 4 th , 8 th , 16 th , and 24 th h. Sedation was measured according to Ramsay sedation scale. VAS Scores were significantly lower in the Group P compared with Group D at 8 th , 16 th , and 24 th h (P < 0.001). Sedation score were statistically higher in the Group D compared with Group P at 4 th , 8 th , 16 th , 24 th h (P < 0.006) as shown in [Table 4].
Table 4: Post-operative analgesia and sedation score

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   Discussion Top


During laparoscopic surgical procedures changes in patient's position and the surgical stress, especially following pneumoperitoneum cause labile hemodynamics. The choice of anesthetic technique for upper abdominal laparoscopic surgery is mostly related to general anesthesia with muscle relaxation, tracheal intubation, and intermittent positive pressure ventilation. [1] This study was conducted in 80 adult patients belonging to ASA-PS-I to evaluate the effect of IV Paracetamol and Dexmedetomidine infusion on peri-operative hemodynamic response and the post-operative analgesia in the laparoscopic cholecystectomy.

According to New South Wales Therapeutic Advisory Group Current Opinion October 2005, the recommended dose of Paracetamol is 1 g IV up to 4 times daily with a minimum interval between each dose at least 4 h in adults. [7] At recommended dosages Paracetamol is not associated with the increased incidence of nausea, vomiting, and respiratory depression observed with opioids. Furthermore, Paracetamol due to its different action mechanism interferes neither with platelet nor kidney function. Its analgesic action is not clear although its central level action has been hypothesized. [3] Because of the lower adverse events compared to NSAIDs, Paracetamol be the preferred choice for peri-operative baseline analgesia. [8] Paracetamol does enhance analgesic efficacy when added to NSAIDs compared to NSAIDs alone.

Dexmedetomidine, and α-2 adrenoreceptor agonist is approved for sedation of initially intubated and mechanically ventilated patients by continuous infusion for only less than 24 h in intensive care setting. α-2 adrenoceptor agonists are being increasingly used in anesthesia and critical care as they not only decrease sympathetic tone and attenuate the stress responses to anesthesia and surgery; but also cause sedation, analgesia, and anxiolysis. The bolus of 1 μg/kg Dexmedetomidine initially results in a transient increase of the blood pressure and a reflex fall in HR, especially in younger, healthy patients. [9] Given the propensity of the drug to produce hypotension and or bradycardia when it is administered to volunteers or patients, it was important to determine an infusion rate that would maximize the anesthetic and analgesic sparing effect although, minimizing the occurrence of adverse cardiovascular side-effects requiring therapeutic intervention. Jung et al. in their comparative study showed significant advantage of Dexmedetomidine at dose of 1 μg/kg bolus followed by 0.2-0.7 μg/kg/h infusion for 24 h. [10] It is a safe sedative alternative to benzodiazepine/opioid combination in patients undergoing monitored anesthesia care for a multitude of procedures because of its analgesic, "co-operative sedation" and lack of respiratory depression properties. [11] Several findings lead to the conclusion that the major sedative and antinociceptive effects of Dexmedetomidine are attributable to its stimulation of the α-2 adrenoceptors in the locus coeruleus.

In our study at a dose of 0.2-0.4 μg/kg infusion had a significant hemodynamic stability over post-operative h, which corroborates with the study done by Jung et al. in a prospective randomized double blind study compared the effects of Dexmedetomidine and remifentanil on hemodynamic stability, sedation and post-operative pain control in PACU with the Dexmedetomidine at a dose of 1 μg/kg IV over 10 min followed by 0.2-0.7 μg/kg/h continuous IV infusion had a significant advantage in terms of post-operative hemodynamic stability. [10]

Talke et al. in 1995 in their study showed that both HR and SBP reduced in response to the 1 h Dexmedetomidine infusion to the targeted plasma conc. of 0.45 ng/ml, which appears to benefit peri-operative hemodynamic management in patients undergoing vascular surgery. [12]

In another study, Talke et al. administered Dexmedetomidine infusion for its ability to attenuate stress responses during emergence from anesthesia after major vascular operation and found that Dexmedetomidine attenuates increase in HR and plasma noradrenaline concentration during emergence from anesthesia, which is supporting the hemodynamic finding in our study. [13]

In our study, we found post-operative pain and sedation score in Group D remained significantly in acceptable range. Our study is also supported by Jung who found that the hemodynamic stability remained normal in post-operative period and demonstrated good pain control with patient awareness. [10]

Cattabriga et al. administered 1 g of Paracetamol pre-medication and highlighted the fact that Paracetamol has a good analgesic action by studying the 1 st 30 h- deep breathe VAS score, which were significantly lower. With this idea, in our study, we used 1 g Paracetamol and found that VAS score was significantly lower in Group P than Group D at 8 th , 16 th , 24 th , post-operative hours. [3]

Salihoglu described that there is superior pain control and significant reduction of time to 1 st rescue medication and also the total consumption of rescue medication with fewer side effects. Similarly, in our study, we found that there was significant lower VAS score in Group P than Group D and there was minimum requirement of rescue analgesic. [14]

 
   References Top

1.Jean JL. Anesthesia for laparoscopic surgery. In: Miller RD editor. Miller′s Anesthesia. 7 th ed. Churchill Livingstone: Elsevier; 2010. p. 2189-93.  Back to cited text no. 1
    
2.Kehlet H, Dahl JB. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anesth Analg 1993;77:1048-56.  Back to cited text no. 2
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3.Cattabriga I, Pacini D, Lamazza G, Talarico F, Di Bartolomeo R, Grillone G, et al. Intravenous Paracetamol as adjunctive treatment for postoperative pain after cardiac surgery: A double blind randomized controlled trial. Eur J Cardiothorac Surg 2007;32:527-31.  Back to cited text no. 3
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4.Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression. Proc Natl Acad Sci U S A 2002;99:13926-31.  Back to cited text no. 4
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5.Bonnefont J, Courade JP, Alloui A, Eschalier A. Antinociceptive mechanism of action of Paracetamol. Drugs 2003;63:1-4.  Back to cited text no. 5
    
6.Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, et al. Dexmedetomidine infusion during laparoscopic bariatric surgery: The effect on recovery outcome variables. Anesth Analg 2008;106:1741-8.  Back to cited text no. 6
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7.New South Wales Therapeutic Advisory Group Inc. IV Paracetamol- where does it sit in hospital practice? Curr Opin 2005;4.  Back to cited text no. 7
    
8.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. 8
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9.Bhatia P. Dexmedetomidine: A new agent in anaesthesia and critical care practice, 2002. Available from: http: // www.theiaforum.org/Article_Folder/dexmedetomidine-anaesthesia-critical-care-practice.pdf.   Back to cited text no. 9
    
10.Jung HS, Joo JD, Jeon YS, Lee JA, Kim DW, In JH, et al. Comparison of an intraoperative infusion of Dexmedetomidine or remifentanil on perioperative haemodynamics, hypnosis and sedation, and postoperative pain control. J Int Med Res 2011;39:1890-9.  Back to cited text no. 10
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11.Grewal A. Dexmedetomidine: New avenues. J Anaesthesiol Clin Pharmacol 2011;27:297-302.  Back to cited text no. 11
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12.Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M, et al. Effects of perioperative Dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. Anesthesiology 1995;82:620-33.  Back to cited text no. 12
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13.Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P, et al. The hemodynamic and adrenergic effects of perioperative Dexmedetomidine infusion after vascular surgery. Anesth Analg 2000;90:834-9.  Back to cited text no. 13
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14.Salihoglu Z, Yildirim M, Demiroluk S, Kaya G, Karatas A, Ertem M, et al. Evaluation of intravenous Paracetamol administration on postoperative pain and recovery characteristics in patients undergoing laparoscopic cholecystectomy. Surg Laparosc Endosc Percutan Tech 2009;19:321-3.  Back to cited text no. 14
[PUBMED]    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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