ATTENUATION OF THE PRESSOR RESPONSE TO TRACHEAL INTUBATION IN PREGNANT PATIENTS BY KETOROLAC DURING CAESAREAN SECTION Osama M. Warda*, M.D., Mohamed R. El-Tahan**, M.D., Amr M. Yasseen*, M.D., Magdy M. Attallah*, M.D., AND Mohamed K. Matter 1 , M.D. From the Department of Obstetrics And Gynaecology*, the Department of Anaesthesia And Surgical ICU**, and the Department of Paediatrics 1 , Faculty of Medicine, Mansoura University, Mansoura, Egypt. Objectives: ketorolac may attenuate maternal stress response to tracheal intubation, without subsequent dangers of opioid-induced neonatal depression. The objective of this study is to evaluate the haemodynamic and hormonal effects of pre-emptive ketorolac on surgical stress and the postoperative analgesic consumption, after Cacsarean delivery. Study Design: A prospective randomized double-blinded placebo-controlled study. Methods: After ethical approval, 90 patients scheduled for elective Cacsarean deliveries were randomly allocated U) the ketorolac group (/*=45); received IV ketorolac 15 mg bolus, followed by an infusion of 7.5 mg.lr'.and the saline for placebo group (/;=45). Anaesthesia was maintained with 50% nitrous oxide, 0.5% isoflurane, and vecuronium. The haemodynamic variables and the levels of plasma corlisol were recorded before and after induction, and after delivery, The graded uterine relaxation, the need for supplementary doses of oxylocin, the peri-operative blood loss, bleeding lime, and Apgar scores at 1 and 5 minutes, postoperative pain scores at rest and with movement, and namadol consumptions were assessed. Results: After intubation, parturients receiving ketorolac had a smaller increase in heart rale, systolic and mean arterial blood pressure (P< 0.001) and lower plasma corlisol concentrations, (45± 15.1 vs. 32.2 ± 7.61 Ug. dl"', P<0.05). Therefore, they had lower VAS pain scores al rest and on movement, for the first 2 postoperative hours (P<0.001), later lime to first request for analgesia and less iramadol consumption for the first 4 post-operative hours [0 (0-100) mg vs. 100 (0-100) mg, P = 0.004]. There were no differences between groups with regard to peri-operative blood loss, bleeding lime, transfusion requirements, nausea, vomiting or Apgar scores, with no evidence of premature closure of the ductus arteriosus of the newborns. Conclusion: Pre-emptive ketorolac is safe and effective in attenuating the maternal stress response with improved quality of post-operative analgesia in Caesarean delivery patients. Key words: Anaesthesia, Caesarean section, stress response, ketorolac. catecho]amines after tracheal intubation, in women having Cacsarean delivery, may decrease placenta! perfusion and uterine blood flow by 20%-35% ( K Opioid analgesia gives a very high level of patient satisfaction. Opioids are routinely omitted at the induction of general anaesthesia for Caesarean Corresponding author: Osama M. Warda, MD, Obstetric And Gynaecology Department, Mansoura University, Mansoura, Egypt; E-mail: [email protected]. INTRODUCTION Pain relief of good quality after Caesarean section results in early mobilization and good early mother-child interaction. Increased sympathetic nervous system activity and plasma concentrations of Osama M. Warda, et al- 43 Attenuation of the pressor response
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ATTENUATION OF THE PRESSOR RESPONSE TO TRACHEAL INTUBATION IN PREGNANT
PATIENTS BY KETOROLAC DURING CAESAREAN SECTION
Osama M. Warda*, M.D., Mohamed R. El-Tahan**, M.D., Amr M. Yasseen*, M.D., Magdy M. Attallah*, M.D., AND Mohamed K. Matter1, M.D.
From the Depar tment of Obstetrics And Gynaecology*, the Department of Anaesthesia And
Surgical ICU**, and the Department of Paediatrics1 , Faculty of Medicine, Mansoura University,
Mansoura , Egypt.
Objectives: ketorolac may attenuate maternal stress response to tracheal intubation, without subsequent dangers of opioid-induced neonatal depression. The objective of this study is to evaluate the haemodynamic and hormonal effects of pre-emptive ketorolac on surgical stress and the postoperative analgesic consumption, after Cacsarean delivery. Study Design: A prospective randomized double-blinded placebo-controlled study. Methods: After ethical approval, 90 patients scheduled for elective Cacsarean deliveries were randomly allocated U) the ketorolac group (/*=45); received IV ketorolac 15 mg bolus, followed by an infusion of 7.5 mg.lr'.and the saline for placebo group (/;=45). Anaesthesia was maintained with 50% nitrous oxide, 0.5% isoflurane, and vecuronium. The haemodynamic variables and the levels of plasma corlisol were recorded before and after induction, and after delivery, The graded uterine relaxation, the need for supplementary doses of oxylocin, the peri-operative blood loss, bleeding lime, and Apgar scores at 1 and 5 minutes, postoperative pain scores at rest and with movement, and namadol consumptions were assessed. Results: After intubation, parturients receiving ketorolac had a smaller increase in heart rale, systolic and mean arterial blood pressure (P< 0.001) and lower plasma corlisol concentrations, (45± 15.1 vs. 32.2 ± 7.61 Ug. dl"', P<0.05). Therefore, they had lower VAS pain scores al rest and on movement, for the first 2 postoperative hours (P<0.001), later lime to first request for analgesia and less iramadol consumption for the first 4 post-operative hours [0 (0-100) mg vs. 100 (0-100) mg, P = 0.004]. There were no differences between groups with regard to peri-operative blood loss, bleeding lime, transfusion requirements, nausea, vomiting or Apgar scores, with no evidence of premature closure of the ductus arteriosus of the newborns. Conclusion: Pre-emptive ketorolac is safe and effective in attenuating the maternal stress response with improved quality of post-operative analgesia in Caesarean delivery patients. Key words: Anaesthesia, Caesarean section, stress response, ketorolac.
catecho]amines after tracheal intubation, in women
having Cacsarean delivery, may decrease placenta!
perfusion and uterine blood flow by 20%-35%( K
Opioid analgesia gives a very high level of patient
satisfaction. Opioids are routinely omitted at the
induction of general anaesthesia for Caesarean
Corresponding author: Osama M. Warda, MD, Obstetric And Gynaecology Department, Mansoura University, Mansoura, Egypt; E-mail: [email protected].
INTRODUCTION Pain relief of good quality after Caesarean section
results in early mobilization and good early
mother-child interaction. Increased sympathetic
nervous system activity and plasma concentrations of
Osama M. Warda, et al- 43 Attenuation of the pressor response
of the patent ductus artenosus when given in large
doses to mothers before delivery. In the current
study, there was no reported evidence of premature
closure of the ductus artenosus or pulmonary
hypertension of the newborns in both groups.
Similarly, several studies reported no difference in
neonatal outcome, as determined by Apgar scores
and blood gas analyses with the pre-operative use of
IV tenoxicam or postoperative Caesarean delivery
pairi relief*23^. Vermillion and others' reported that in
61 Cases in which the pregnant women were treated
for preterm labor with indomethacin (25 mg orally
every 6 hours), a dramatic yet reversible increase in
the incidence of indomelhacin-induced ductal
constriction occurs at 31 weeks' gestation. However,
after discontinuation of indomethacin therapy, all
follow-up cchocardiograms demonstrated a return to
non-constricted ductal flow velocities, with no
significant adverse neonatal ou tcomes^) . Moreover,
the transfer of ketorolac into breast milk has been
quantified, and it is considered to be safe for use
during lactation*25). Thus, a possible explanation
could be thai, we used relatively small doses of
ketorolac for limited periods of continuous IV
infusion.
In conclusion, in this study pre-emptive IV
ketorolac is safe and effective in attenuating the
maternal stress response with improved the quality of
post-operative analgesia in Caesarean delivery
patients, with no adverse neonatal outcome.
Limitations to our study:
Further muki-center studies are needed to define
the efficacy and the safely of the use of pre-operative
ketorolac in pregnant patients undergoing Caesarean
delivery for the attenuation of the stress response and
evaluate the neonatal outcome.
1. Gin T. O'Mcara ME. Kan AF. Leung RKW. ci al: Plasma caiccholami ncs and neonatal condition alter induction of anaesthesia with propofol or ihiopcmono at Caesarean section. Br .1 Anaesth 1993; 70:311-317.
2. Gin T. Ngan-Kee WD. Sin YK. Smart JC. el al: Alfentanil given immediately before the induction of anesthesia for elective Ccsarean delivery. Anesth Analg 2000;90:1167-1172.
3. Olofsson Cl, Legcby MH, Nygards EB, and Osiman KM: Diclofcnac in the treatment of pain after Caesarean delivery. An opioid-saving strategy. Eur .1 Obstei Gynccol Rcprod Biol 2000; 88(2): 143-149.
4. El-Hakim M and Nafie M: I.v. tenoxicam for analgesia during Caesarean section. Br J Anacsih 1995;74:643-646.
5. Gillis JC and Brogdcn RN: Ketorolac: A reappraisal of ils pharmacodynamic and pharmacokinelic properties and therapeutic use in pain nianaguneiii Drugs 1997; 53: 139-188.
6. Lowcler JL, Shaekelford DP, Holheri D, anil Beste TM: A randomized, controlled trial to compare ketorolac Iromelhamine versus placebo alter Cesarean section to reduce pain and narcotic usage Am J Obstct Gynccol 2003: 189:1559 -1562.
7. Kovac AL: Controlling (he hemodynamic response to laryngoscopy and endotiachcal intubation. J Clin Anesth 1996;8:63-79.
8. Kissin I: Preemptive analgesia: why ils effect is not always obvious. Anesthesiology 1996; 84:1015-1024.
9. Krishna BR, Zakowski Ml, and Grant GJ: Sufcnlanil transfer in the human placenta during in vitro pcrfusion. Can J Anacsih 1997; 44(9): 996-1001.
10. El-Hakim M, Falhy A, Amine H. Saecd A. and Mckawy M: Effect of i.v, tenoxicam during Caesarean delivery on platelet activity. Ada Anacslhcsiol Scand 2000; 44(5):555-563.
1 I. Chamhricr C. Chassard D, Bicnvenu J, Saudin F. cl al: Cylokinc and hormonal changes after cholecysleclomy. Effect of ibuprofen prelreaimcnl. AnnSurg 1997 Jul; 226(1): 110-111.
12. Moole CA: The prevention of post operative pain. Can J Anacsih 1994; 41: 527-33.
Osama M. Warda, et al. 49 Allf'im/llinti nflha nrarcnr ••■
13. Gin T, Kan AF, Lam KK, and O'Meara ME: Analgesia after Caesarean section with intramuscular ketorolac or pethidine. Anaesth Intensive Care 1993; 21: 420-423.
14. Jelinek GA: Ketorolac versus morphine for severe pain; Ketorolac is more effective, cheaper, and has fewer side effects. BMJ 2000; 321 (72711:1236-1237.
15. Rusy LM, Houck CS. Sullivan LJ, Ohlms LA, Jones DT, et al: A double-blind evaluation of ketorolac tromethaminc versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth Analg 1995,80,226-229.
16. Jones SF: NSAID for caesarean section. Br J Anaesth 1995: 75:666-669.
17. Thwaites BK, Nigus DB, Bouska GW, Mongan PD, ct al: Intravenous ketorolac tromethaminc does not worsen platelet function during knee arthroscopy under general anesthesia. Anesth Analg 1995; 81, 119-124.
18. Strom BL. Berlin JA. Kinman JL, ct al: Parcntera! ketorolac and risk of gastrointestinal and operative site bleeding: a post-marketing surveillance study. JAMA 1996; 275: 376-382.
19. Tzeng JI and Mok MS: Combination of intramuscular ketorolac and low dose epidura! morphine for the relief of post-Caesarcan pain. Ann
Acad Med Singapore 1994: 23: 10-13.
20. Sia ATH, Thomas E, Chong JL, and Loo CC Combination of suppository diclofenac and inlravenous morphine infusion in post-Caesarcan section pain relief - a step towards balanced analgesia'? Sing Med J 1997; 38: 68-70.
21. Rorarius MGF, Suominen P, Baer GA, et al: Diclofenac and ketoprofen for pain treatment alter elective Caesarean section. Br J Anaesth 1993; 70: 293-300.
22. Mogensen T, Vegger P, Jonsson T, et al: Systemic piroxicam as an adjunct to combined epidural bupivacainc and morphine for postoperative pain relief-a double-blind study. Anesth Analg 1992; 74: 366-370.
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24. Vermiilion ST, Scardo JA, Lashus AG, and Wiles HB: The effect of indomethacin locolysis on fetal ductus arteriosus constriction with advancing gestational age. Am J Obstet Gynccol 1997; 177 (2):256-9: 259-61.
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Table I : Demographic data of the patients in ketorolac group and placebo group. Data are expressed as [mean ± SD].
Second group ( n = 72)
P value
Age (Years) 27.1 ±4.18 26.2 ±5.10
Weight (Kg) 78.6 ± 7.96 77.7 ±10.78
Height (cm) 162 ±3.35 160 ±2.23
Gestational age (weeks) 38.9 ± 1.51 39.3 ± 1.71
I-D lime (.minutes) 11.4 ± 1.76 10.8 ±1.47
Anaesthesia time (minutes) 39.7 ± 5.26 41.8 ±5.63
Birth weight (Kg) 3.3 ±0.26 3.2 ±0.19
I-D time = Induction to delivery time (minutes)
* Significant when P < 0.05.
Table II : Visual analogue scale (VAS) assessment of post-operative pain, at rest and with movement in the studied groups. Data are expressed as [median (range)].
PI acebo group Ketorol ac group (n = 45) (n = = 45)
* F < 0.05 Significmn when compared with the placebo group.
Osama M. Wurdu, el al. 51 Alli'iiiuilion of the I'rcxsor iv.v/n'ii.vc
Table III : The time to first request for analgesia, the post-operative hourly tramadol consumption. and verbal rating score (VRS) for sedation in the studied groups. Data are expressed as [mean + SD or median (range)].
Placebo group Ketorolac group P value (n = 45) ( n = 45)
The time to first request for analgesia (hours) 1.2 ±0.94 3.0+ 1.45 0.001* The postoperative hourly tramadol consumption (mg)
* P < 0.05 Signifieatn when compared with the placebo group.
Table VI : The Peri-operative data. Data are expressed as [median (range), percentage % (numbers) or mean ± SD].
Placebo group Ketorolac group P value ( n = 45) ( n = 45)
VAS assessment of uterine relaxation 3 (0 - 3) 3 (0 - 3) 0.851 Percentage of the patients needed 11.1% (5/45) 15.6(7/45) 0.772 supplementary doses of oxytocin (i.u) The intra-operative blood loss (ml) 279 + 88.97 298 ± 89.95 0.557 The postoperative blood loss 0 ( 0 - 2 ) 0 ( 0 - 3 ) 1.000 BT (minutes): Pre-opcraiive 3.6 ± 1.24 3.4 ± 1.18 0.655
Post-operative 3.7+ 1.05 3.7 ±0.96 0.857 Percentage of the patients suffered from nausea 11.1% (5/45) 6.7% (3/45) i.ooo ; and vomiting The post-operative score for nausea and vomiting
P < 0.05 vSignillcain when compared with (he placebo group.
Eiiypt..]. Fertil. Sferil. 52 January. 2007, Vol. II. No. 1
160
140
120
100 D l
E E 80 a. m co 60
40
20
0
0
Placebo group
Ketorolac group
3 4 5 Post-induction
6 10 15 30 Postoperative Post-delivery
Time (minutes)
* P< 0.05 when compared with placebo group.
Figure (!): Perioperalive hearl rale [Bpm] changes in the studied group [mean ± SD).
—♦— Placebo group
Ketorolac group
O 1 3 4 5 Post-induction
6 10 15 30 Postoperative Post-delivery
Time (minutes)
P< 0.05 when compared with placebo group.
Fig. 2. Perioperalive systolic arterial blood pressure (SBP) [mmHg] changes in the studied groups [mean ± SDJ.
Osama M. Warda, et al. 53 Attenuation of the pressor response
120
100
80
: | 60 E a. < 40
20
Placebo group
Ketorolac group
0 1 2 3 4 5 6 1 0 15 30 Postoperative
Post-induction Post-delivery
Time (minutes)
* P< 0.05 when compared with placebo group. 7igure (3): Perioperalive mean arterial blood pressure (MAP) [mmHg] changes in the studied groups [mean ± SD|.
—♦— Placebo group
-9— Ketorolac group
Preoperative 5 min post-induction 1h after delivery
Time
P< 0.05 when compared with placebo group.
Fig. 4. Scrum cortisol level changes in the studied groups. Data arc expressed as [mean ±SD].
Egypt. J. Fertil. Steril. 54 January, 2007, Vol. II. No. I