- Email: [email protected]
Post cesarean analgesia with ketorolac tromethamine and uterine atonia
ELSEVIER
European Journal of Obstetrics & Gynecology and Reproductive Biology 72 (1997) 205 206
.
.
.
GYNE .
.
.
.
.
.
~
. . . . . .
o
. . . .
Case report
Post cesarean analgesia with ketorolac tromethamine and uterine atonia Pierre Diemunsch ~, Martine Alt
b
Anne-Marie Diemunsch ~, Alain Treisser d,,
" Deparlement d'Ane.~thesiologie, [email protected] Universitaire.s ,le Stra.shourg, I. phtee de l'H@ital, 67000 Strasbourg, Franee b Centre de PharmacoviL, ilanee Alsace, H@itaux Uttiversilaires de S[rashourg, 1, place de l'H@ital, 67000 SlrasbourL,, France Faeulte; de Pharmacie, 67000 Strashour~, France d Maternity; Eeo/e de Sages Femmes, H@itaux Uni~ersilairev de Slrasboure, 1, place de l'H@ital, 67000 Slras hourL,, France
Received 5 June 1996; received in revised form 19 August 1996; accepted 22 November 1996
Abstract
Post cesarean analgesia with ketorolac tromethamine may contribute to promote uterine atonia where important risk factors, as in this case twin gestation and performance of a myomectomy, are already present. © 1997 Elsevier Science Ireland Ltd.
Keywords: Complications; Ketorolac tromethamine: Post cesarean section analgesia
I. Introduction
2. Case report
Ketorolac tromethamine is a non-steroidal anti-infla m m a t o r y drug (NSAID) of the pyrrolacetic acid family proposed for post-operative analgesia, the main advantage being the lack of opioid-related side effects. By the intramuscular (|M) route, the analgesic potency of ketorolac tromethamine 30 mg is equivalent to that of morphine 12 mg [1] or pethidine 75 mg [2]. The initial recommended dosage was 30 mg every 4 6 h without exceeding 120 mg/day or 5 days of treatment. Bioavailability and dosages are similar by the intravenous (IV) route [4]. Ketorolac has recently been proven effective for post caesarean section analgesia [2]. We would like to report a case of serious uterine hypotonia and bleeding occurring after a single 30 mg IV dose of this prostaglandin synthesis inhibitor administered for post caesarean section pain.
An elective caesarean section was carried out on a 39-year-old primipara after 37 weeks of gestation. The pregnancy involved twins and was complicated by foetal hypotrophy. Past medical history included allergy to fl-lactams and pruritic urticarial papules and plaques of pregnancy (PUPPP), confirmed by cutaneous biopsy at 35 weeks of amenorrhea. The operation was performed under lumbar epidural anaesthesia (bupivacaine 0.5%, 55 mg; lidocaine 2%, 160 mg; fentanyl, 50 mcg; analgesia level, thoracic 4). The lower uterine segment incision was carried out following a Pfannenstiel parietal incision. Both extractions were breech, following version of the second twin. The neonates, both male, weighed 2440 and 2150 g, respectively and had 1 and 5 min Apgar scores of 10. Separation of the anterior, single, bichorial, biamniotic placenta was uneventful. Uterine contraction with oxytocm infusion (ten units in 500 ml of 10% dextrose over 30 min), was satisfactory. Blood loss was estimated as
*Corresponding author. Tel.: +33 388116819 (ext. 17612); lax: + 33 388116299.
0301-2115/97/$17.00 ' ( 1997 Elsevier Science Ireland Ltd. All rights reserved. PII S0301-2 11 5(96}112682-6
206
P. Diemunsch et ul. European Journal o! Oh,stetrics & Gvnecolo~(v amt R~7)rm&ctice Biology 72 (1997) 205 206
400 ml and intraoperative urine output was 100 ml. The operation also involved the resection of a small subserous pedunculated myoma, in a necrobiotic state (4 x 3 × 2 cm) located on the right anterolateral surface of the uterus. The procedure lasted a total of 1 h 40 min. The post operative analgesia consisted of IV propacetamol (a paracetamol pro-drug, 2 g in 5% dextrose. 50 ml) and ketorolac tromethamine (30 mg in 5% dextrose, 50 ml) infused over 10 min. Sudden haemorrhage occurred 2 h after these infusions (systolic blood pressure, 50 mmHg; haemoglobin, 5.7 g/dl; red cells, 1.9 M/l, haematocrit. 17.2%). Examination revealed severe uterine atonia with the uterine fundus 4 cm above the umbilicus and significant vaginal blood loss. The uterine atonia did not respond to 20 units of IV oxytocin and required administration of 500 meg of sulprostone IM. The blood loss was treated with three units of red cells, 1000 ml of human albumin (4'7,, solution) and 1000 ml of Ringer's solution. The patient progressed satisfactorily in the following few hours.
circumstances promoting uterine inertia (such as uterine over-distention, surgical incision, sepsis, previous history of atonia, prolonged oxytocin infusion during labour). Uterine atonia has been reported following the administration of another NSAID, diclofenac, as a post operative analgesic [5]. That study stressed the need to administer larger doses of oxytocics (methergine) in patients treated with NSAIDs, compared with their placebo group. We consider that the increased need for oxytocics in that study, and our experience, fits in well with the hypothesis of a NSAID uterine relaxing effect.
4. Conclusions
This is the first report of a major post partum hemorrhage and uterine atonia associated with ketorolac tromethamine analgesia after cesarean section. We believe that it may be better to avoid the use of NSAIDs as post-operative analgesics where important risk factors for uterine atonia are already present.
3. Discussion
Ketorolac has been shown to inhibit platelet aggregation, and thromboxane production, prolonging bleeding time by a factor of 1.35 [3,6]. In this case of life threatening bleeding, atonia seems to be the main factor involved since uncomplicated recovery followed sulprostone administration alone, without platelets transfusion. Nevertheless, participation of a ketoroac induced clotting disorder cannot be excluded due to the lack of repeated bleeding time estimations. One could explain the uterine atonia which followed the cesarean section in terms of: (1) an 'at risk' obstetric patient having (a) multifetal gestation and (b) concurrent myomectomy; and (2) the post operative analgesic medications resulting in inhibition of prostaglandin synthesis. Contraction of the uterus, immediately after delivery, requires the stimulating effect of oxytocin and of prostaglandins (in particular PGF2-c~ and PGE2), whose production increases at that time. This humoral activation is even more crucial in cases associated with
References [1] Brown CR, Mazzulla JP, Moks MS, Nussdorf RT, Rubin PD, Schwesinger WH. Comparison of repeat doses of intramuscular ketorolac tromethamine and morphine sulfate for analgesia after major usrgery. Pharmacotherapy 1990:10(6 Pt 2): 45S 50S. [2] Gin T, Kan AF. Lam KK, O'Meara ME. Analgesia after caesarean section with intramuscular ketorolac or pethidine. Anaesth Intensive Care 1993: 21:420 423. [3] Read JR, Bainton R. Operative haemorrhage m association with ketorolac. Anaesthesia 1994:49(1 ): 73 74 [4] Ready LB, Brown CR, Stahlgren LH, Egan KJ. Ross B, Wild L, Moodie JE, Jones SF, Tommeraasen M, Trierwieler M. Evaluation of intravenous Ketorolac administered by bolus or infusion fnr treatment of postoperative pain. Anesthesiology 1994; 80: 1277 1286. [5] Roarius MFG, Suominen P, Baer GA, Romppanen O. Tuimala R. Diclofenac and ketoprofen for pain treatment after elective caesarean section. Br J Anaesth 1993: 70:293 297. [6] Toon S, Holt BL. Mullins FGP, Bllingham R. Aarons L, Rowland M. Investigations into the potential effects of multiple dose ketorolac on the pharmacokinetics and pharmacodynamics of racemic warfarin. Br J Clin Pharmacol 1990: 30:743 750.
European Journal of Obstetrics & Gynecology and Reproductive Biology 72 (1997) 205 206
.
.
.
GYNE .
.
.
.
.
.
~
. . . . . .
o
. . . .
Case report
Post cesarean analgesia with ketorolac tromethamine and uterine atonia Pierre Diemunsch ~, Martine Alt
b
Anne-Marie Diemunsch ~, Alain Treisser d,,
" Deparlement d'Ane.~thesiologie, [email protected] Universitaire.s ,le Stra.shourg, I. phtee de l'H@ital, 67000 Strasbourg, Franee b Centre de PharmacoviL, ilanee Alsace, H@itaux Uttiversilaires de S[rashourg, 1, place de l'H@ital, 67000 SlrasbourL,, France Faeulte; de Pharmacie, 67000 Strashour~, France d Maternity; Eeo/e de Sages Femmes, H@itaux Uni~ersilairev de Slrasboure, 1, place de l'H@ital, 67000 Slras hourL,, France
Received 5 June 1996; received in revised form 19 August 1996; accepted 22 November 1996
Abstract
Post cesarean analgesia with ketorolac tromethamine may contribute to promote uterine atonia where important risk factors, as in this case twin gestation and performance of a myomectomy, are already present. © 1997 Elsevier Science Ireland Ltd.
Keywords: Complications; Ketorolac tromethamine: Post cesarean section analgesia
I. Introduction
2. Case report
Ketorolac tromethamine is a non-steroidal anti-infla m m a t o r y drug (NSAID) of the pyrrolacetic acid family proposed for post-operative analgesia, the main advantage being the lack of opioid-related side effects. By the intramuscular (|M) route, the analgesic potency of ketorolac tromethamine 30 mg is equivalent to that of morphine 12 mg [1] or pethidine 75 mg [2]. The initial recommended dosage was 30 mg every 4 6 h without exceeding 120 mg/day or 5 days of treatment. Bioavailability and dosages are similar by the intravenous (IV) route [4]. Ketorolac has recently been proven effective for post caesarean section analgesia [2]. We would like to report a case of serious uterine hypotonia and bleeding occurring after a single 30 mg IV dose of this prostaglandin synthesis inhibitor administered for post caesarean section pain.
An elective caesarean section was carried out on a 39-year-old primipara after 37 weeks of gestation. The pregnancy involved twins and was complicated by foetal hypotrophy. Past medical history included allergy to fl-lactams and pruritic urticarial papules and plaques of pregnancy (PUPPP), confirmed by cutaneous biopsy at 35 weeks of amenorrhea. The operation was performed under lumbar epidural anaesthesia (bupivacaine 0.5%, 55 mg; lidocaine 2%, 160 mg; fentanyl, 50 mcg; analgesia level, thoracic 4). The lower uterine segment incision was carried out following a Pfannenstiel parietal incision. Both extractions were breech, following version of the second twin. The neonates, both male, weighed 2440 and 2150 g, respectively and had 1 and 5 min Apgar scores of 10. Separation of the anterior, single, bichorial, biamniotic placenta was uneventful. Uterine contraction with oxytocm infusion (ten units in 500 ml of 10% dextrose over 30 min), was satisfactory. Blood loss was estimated as
*Corresponding author. Tel.: +33 388116819 (ext. 17612); lax: + 33 388116299.
0301-2115/97/$17.00 ' ( 1997 Elsevier Science Ireland Ltd. All rights reserved. PII S0301-2 11 5(96}112682-6
206
P. Diemunsch et ul. European Journal o! Oh,stetrics & Gvnecolo~(v amt R~7)rm&ctice Biology 72 (1997) 205 206
400 ml and intraoperative urine output was 100 ml. The operation also involved the resection of a small subserous pedunculated myoma, in a necrobiotic state (4 x 3 × 2 cm) located on the right anterolateral surface of the uterus. The procedure lasted a total of 1 h 40 min. The post operative analgesia consisted of IV propacetamol (a paracetamol pro-drug, 2 g in 5% dextrose. 50 ml) and ketorolac tromethamine (30 mg in 5% dextrose, 50 ml) infused over 10 min. Sudden haemorrhage occurred 2 h after these infusions (systolic blood pressure, 50 mmHg; haemoglobin, 5.7 g/dl; red cells, 1.9 M/l, haematocrit. 17.2%). Examination revealed severe uterine atonia with the uterine fundus 4 cm above the umbilicus and significant vaginal blood loss. The uterine atonia did not respond to 20 units of IV oxytocin and required administration of 500 meg of sulprostone IM. The blood loss was treated with three units of red cells, 1000 ml of human albumin (4'7,, solution) and 1000 ml of Ringer's solution. The patient progressed satisfactorily in the following few hours.
circumstances promoting uterine inertia (such as uterine over-distention, surgical incision, sepsis, previous history of atonia, prolonged oxytocin infusion during labour). Uterine atonia has been reported following the administration of another NSAID, diclofenac, as a post operative analgesic [5]. That study stressed the need to administer larger doses of oxytocics (methergine) in patients treated with NSAIDs, compared with their placebo group. We consider that the increased need for oxytocics in that study, and our experience, fits in well with the hypothesis of a NSAID uterine relaxing effect.
4. Conclusions
This is the first report of a major post partum hemorrhage and uterine atonia associated with ketorolac tromethamine analgesia after cesarean section. We believe that it may be better to avoid the use of NSAIDs as post-operative analgesics where important risk factors for uterine atonia are already present.
3. Discussion
Ketorolac has been shown to inhibit platelet aggregation, and thromboxane production, prolonging bleeding time by a factor of 1.35 [3,6]. In this case of life threatening bleeding, atonia seems to be the main factor involved since uncomplicated recovery followed sulprostone administration alone, without platelets transfusion. Nevertheless, participation of a ketoroac induced clotting disorder cannot be excluded due to the lack of repeated bleeding time estimations. One could explain the uterine atonia which followed the cesarean section in terms of: (1) an 'at risk' obstetric patient having (a) multifetal gestation and (b) concurrent myomectomy; and (2) the post operative analgesic medications resulting in inhibition of prostaglandin synthesis. Contraction of the uterus, immediately after delivery, requires the stimulating effect of oxytocin and of prostaglandins (in particular PGF2-c~ and PGE2), whose production increases at that time. This humoral activation is even more crucial in cases associated with
References [1] Brown CR, Mazzulla JP, Moks MS, Nussdorf RT, Rubin PD, Schwesinger WH. Comparison of repeat doses of intramuscular ketorolac tromethamine and morphine sulfate for analgesia after major usrgery. Pharmacotherapy 1990:10(6 Pt 2): 45S 50S. [2] Gin T, Kan AF. Lam KK, O'Meara ME. Analgesia after caesarean section with intramuscular ketorolac or pethidine. Anaesth Intensive Care 1993: 21:420 423. [3] Read JR, Bainton R. Operative haemorrhage m association with ketorolac. Anaesthesia 1994:49(1 ): 73 74 [4] Ready LB, Brown CR, Stahlgren LH, Egan KJ. Ross B, Wild L, Moodie JE, Jones SF, Tommeraasen M, Trierwieler M. Evaluation of intravenous Ketorolac administered by bolus or infusion fnr treatment of postoperative pain. Anesthesiology 1994; 80: 1277 1286. [5] Roarius MFG, Suominen P, Baer GA, Romppanen O. Tuimala R. Diclofenac and ketoprofen for pain treatment after elective caesarean section. Br J Anaesth 1993: 70:293 297. [6] Toon S, Holt BL. Mullins FGP, Bllingham R. Aarons L, Rowland M. Investigations into the potential effects of multiple dose ketorolac on the pharmacokinetics and pharmacodynamics of racemic warfarin. Br J Clin Pharmacol 1990: 30:743 750.