Anesth Pain Med 2012; 7: 136～141 ￭Clinical Research￭
Analgesia after Cesarean section in preeclampsia parturients receiving magnesium sulfate: a retrospective comparison with non-preeclampsia parturients
† Department of Anesthesiology and Pain Medicine, *Seoul National University Bundang Hospital, Seongnam, Seoul National University ‡ Hospital, Boramae Medical Center, Seoul, Korea
Hyo-Seok Na*, Hyun-Bin Kim†, Chong-Soo Kim‡, and Sang-Hwan Do*
Background: Magnesium sulfate (MgSO4) is the first-line therapy Key Words: Cesarean section, Magnesium sulfate, Postoperative for managing preeclampsia in obstetrics. Its perioperative adminis- pain, Preeclampsia. tration has been proved to be an effective analgesic adjuvant, which we investigated in parturients undergoing Cesarean section (C-sec). Methods: A retrospective chart review examined 504 parturients INTRODUCTION who underwent C-secs between June 2006 and August 2010, including normal parturients (group N, n = 401) and those diagnosed In parturients with preeclampsia, magnesium sulfate (MgSO4) with preeclampsia (group P, n = 103). A postoperative numeric is the first choice drug for the prevention of eclamptic rating scale (NRS) was used to assess pain, and the number of seizures. It is administered routinely via a loading dose and rescue analgesic administrations and frequency of transfusions were investigated. Perioperative magnesium concentrations were recor- continuous infusion with a target serum concentration of 2− ded for patients in group P. 3.5 mmol/L during the antepartum period and is continued Results: Patients in group P had longer operation and anesthesia until at least 24 h postpartum [1]. times, and more postoperative admission days than those in group Magnesium acts as an N-methyl-D-aspartate (NMDA) recep- N. The NRS of pain was significantly lower in group P at postopera- tive day (POD) 1 (4 vs. 5, P ＜ 0.001), and the frequency of rescue tor antagonist, therefore, it may inhibit induction and mainte- drug administration was lower in group P at POD 1 (36.0% vs. nance of central sensitization from nociceptive stimuli [2]. ＜ 80.3%, P 0.001) and POD 2 (9.7% vs. 21.1%, P = 0.005) than Tramer et al. [3] and many other investigators [4,5] have in group N. Red blood cell transfusions were given more frequently in group P (21.4% vs. 2%, P ＜ 0.001). Pre- and postoperative reported that MgSO4 can be an effective postoperative anal- serum magnesium concentrations in group P were 2.2 (0.5) and gesic adjuvant in a wide spectrum of surgical patients with the 2.1 (0.6) mmol/L, respectively. reduction of rescue analgesic requirement. Conclusions: Postoperative pain after C-sec was less severe and Optimal postoperative pain management is essential for early intravenous patient-controlled analgesia was more efficacious in the preeclampsia group than in the non-preeclampsia group. These and satisfactory recovery from surgery. Moreover, obstetric findings likely resulted from peripartum intravenous MgSO4 admini- patients who undergo Cesarean sections (C-secs) differ slightly stration in the preeclampsia group. (Anesth Pain Med 2012; 7: from general patients. They must care for their babies at 136∼141) immediate postoperative period, raising concern over the use of large doses of analgesic drugs, especially during breastfeeding. In contrast to the numerous investigations proving the
Received: January 16, 2012. analgesia-potentiating effect of MgSO4, no studies have Revised: January 30, 2012. evaluated labor and postoperative pain severity in preeclampsia Accepted: February 27, 2012. parturients receiving MgSO , and comparative prospective or Corresponding author: Sang-Hwan Do, M.D., Ph.D., Department of 4 Anesthesiology and Pain Medicine, Seoul National University Bundang retrospective studies are lacking. We hypothesized that parturi- Hospital, 300, Gumi-dong, Bundang-gu, Seongnam 463-802, Korea. Tel: ents with preeclampsia who received MgSO4 therapy would 82-31-787-7501, Fax: 82-31-787-4063, E-mail: [email protected] experience less severe postoperative pain than patients without American Society of Anesthesiology meeting, 2011, Chicago, USA JSOAP, preeclampsia, and consequently, that less analgesic drugs would 2011, Yokohama, Japan. be required after C-sec.
136 Hyo-Seok Na, et al：Analgesia with MgSO4 after Cesarean section 137
We performed this retrospective study by grouping the lization period, adverse events from intravenous PCA, posto- parturients who underwent C-sec into two groups (preeclampsia perative administration of additional oxytocin, transfusion fre- and non-preeclampsia) and comparing the impact of periope- quency, and recruited parturients characteristics were investi- rative MgSO4 administration on postoperative pain severity gated. Serum magnesium concentrations during the pre- and between the groups. postoperative periods were available only for group P.
Statistical analysis MATERIALS AND METHODS Data were reported as the mean ± SD, median (interquartile This study was approved by the Institutional Review Board range) or number (%). All variables were tested for normal (December 2010; B1012/117−104) and was exempted from the distribution using the Kolmogorov-Smirnov test (result not need to obtain informed patient consent. Data were collected shown) and analyzed with Student’s t-test or the Chi-square and stored without identifying individual patients. This study was test, as appropriate. P values ＜ 0.05 indicated statistical signi- registered at Clinical trials (registration number: NCT01360060). ficance. The statistical analyses were conducted with SPSS software (ver. 15.0; SPSS Inc., Chicago, IL, USA). Data source
Parturients who underwent C-sec deliveries were identified RESULTS retrospectively as ‘antenatal care in normal pregnancy’ (code Z34.0, Z34.8, Z34.9) and ‘preeclampsia’ (code O14.0, O14.1, Enrolled parturients, patients’ characteristics, and ane- O14.9) in the medical database, which was digitally archived sthetic and surgical factors from June 2006 to August 2010. The diagnostic criteria ‘preeclampsia’ included from mild to severe preeclampsia Of the 584 parturients who underwent C-secs between June parturients. Of those, the parturients not treated with MgSO4 2006 and August 2010, 504 were finally included in this perioperatively were taken out of the study, and other exclu- study: 103 in group P and 401 in group N (Fig. 1). All sion criteria were missing medical records, multiple gestation, parturients, who were recruited to group P, received MgSO4 severe postpartum bleeding requiring surgical management or for managing preeclampsia. The age and height of parturients radiological intervention, postoperative intensive care unit mana- did not differ significantly between the groups at the time of gement, postoperative use of epidural patient-controlled analge- operation. Perioperative weight could not be compared because sia (PCA) use, and non-use of postoperative intravenous PCA. the data were updated automatically with the most recent All subjects were divided into two groups based on their measurement. The total operation and anesthesia times, and the diagnosis. Group P included parturients diagnosed with preec- postoperative hospitalization period were longer for group P lampsia who were given MgSO4 perioperatively. The MgSO4 than group N. In both groups, spinal anesthesia was the administration protocol for preeclampsia parturients at our predominant type of anesthesia, and general or epidural hospital was 4 g of MgSO4 in 200 ml of 5% dextrose solu- anesthesia was performed in the remaining parturients. The tion infused intravenously for 15 min, followed by continuous types of anesthesia did not differ significantly between the intravenous infusion of MgSO4 at 1−2 g/h during the peripar- groups (Table 1). tum period. Group N comprised the parturients diagnosed as Serum magnesium level of Group P normal pregnancies. In the course of C-sec, all parturients received ocytocin 30 units intravenously after placenta removal. The serum magnesium level in group P was 2.2 ± 0.5 mmol/L before C-sec, and 2.1 ± 0.6 mmol/L on POD 1. Variables of interest Postoperative pain, rescue analgesics, and intrave- The primary outcome parameter was the numeric rating scale nous PCA (NRS) score (0−10) for postoperative pain during the posto- perative admission period [postoperative days (POD) [1-4]. The The NRS scores of pain on POD 1, 2, and 3 were secondary outcome parameter was the number of patients significantly lower in group P than in group N [4 (4-6) vs. 5 requiring postoperative rescue analgesics. In addition, the type (4-5), P ＜ 0.001 on POD 1; 4 (3-4) vs. 4 (3-5), P = 0.01 of anesthesia, duration of anesthesia and operation, hospita- on POD 2; 3 (3-3) vs. 3 (2-4), P = 0.032 on POD 3 (Table 138 Anesth Pain Med Vol. 7, No. 2, 2012
Fig. 1. Flow chart of patient enrollment.
Table 1. Patients’ Characteristics, Anesthetic and Surgical Factors fentanyl, morphine, or nalbuphine, with or without ketorolac, and the intravenous PCA was set to deliver the analgesics as Group N Group P P value a continuous background infusion plus patient-controlled bolus (n = 401) (n = 103) injections. Of the adverse events associated with intravenous Age (yr) 28.4 ± 3.6 27.5 ± 5.0 0.06 PCA in group N, nausea or vomiting was the most frequent Height (cm) 158.7 ± 14.2 156.0 ± 19.8 0.22 (12.5%), followed by dizziness (7%) and pruritus (1.5%). In Operation time (min) 52.4 ± 17.2 59.7 ± 16.1 ＜0.001 Anesthesia time (min) 83.0 ± 18.2 91.6 ± 24.7 0.001 group P, the parturients showed comparable adverse events of Postoperative admission day 5.3 ± 1.0 6.4 ± 2.6 ＜0.001 nausea or vomiting (11.1%), dizziness (7.3%), and pruritus Type of anesthesia 0.14 (1.6%). Minor side effects, such as bradycardia, hypotension, Spinal 354 (88.3) 85 (82.5) body flushing, and dry mouth, occurred at frequencies below Epidural 28 (7.0) 8 (7.8) General 19 (4.7) 10 (9.7) 1% in both groups.
Data are expressed as mean ± SD or number (%). Group N: Oxytocin use and transfusion parturients diagnosed as normal pregnancy. Group P: parturients diagnosed with preeclampsia. Oxytocin was administered more frequently in group P than in group N during postoperative period (45.5% vs. 16.8%, P ＜ 0.001), and the infused units were greater in group P (20 2, Fig. 2). Moreover, the number of patients requiring postope- ± 28 vs. 5 ± 14 units, P ＜ 0.001). The frequency of intra- rative rescue analgesics was significantly lower in group P and postoperative red blood cell transfusions was significantly than in group N on POD 1 (36.0% vs. 80.3%, P ＜ 0.001) higher in group P than in group N (21.4% vs. 2.0%, P ＜ and POD 2 (9.7% vs. 21.1%, P = 0.005; Table 2). However, 0.001). the NRS score and incidence of rescue analgesic drug administration did not differ significantly between the groups at DISCUSSION POD 3 and 4. Intramuscular ketorolac injection was the most common rescue analgesic drug in both groups (group P: The main finding of this retrospective study was that
91.9%, group N: 90.1%), followed by intramuscular tramadol. parturients who received perioperative MgSO4 for the The main intravenous PCA analgesic in both groups was management for preeclampsia and underwent C-sec showed Hyo-Seok Na, et al：Analgesia with MgSO4 after Cesarean section 139
Table 2. Postoperative Numeric Rating Scale (NRS) of Pain and Number of Rescue Drug Administration
NRS Rescue drug
Group N Group P Group N Group P P value P value (n = 401) (n = 103) (n = 401) (n = 103)
POD 1 5 (4−6) 4 (4−5) ＜0.001 322 (80.3) 37 (36.0) ＜0.001 POD 2 4 (3−5) 4 (3−4) 0.01 85 (21.1) 10 (9.7) 0.005 POD 3 3 (2−4) 3 (3−3) 0.032 38 (9.5) 6 (5.8) 0.165 POD 4 2 (2−3) 2 (2−3) 0.155 18 (4.5) 3 (2.9) 0.333
Data are expressed as median (interquartile range) or number (%). POD: postoperative day. Group N: parturients diagnosed as normal pregnancy. Group P: parturients diagnosed with preeclampsia.
Therefore, magnesium might be able to block central sensitization and attenuate pain. Similar studies of obstetric patients have reported that the administration of ketamine, another NMDA receptor antagonist, during C-sec reduced chronic postsurgical persistent pain at postoperative 2 week
[12], and intrathecal or epidural MgSO4 supplements with local anesthetic drugs had some benefits as an analgesic adjuvant after C-sec [13,14]. Conversely, some clinical reports have shown that magnesium had little or no additive effects as an analgesic adjuvant [15,16]. In one report targeting obstetric patients who
Fig. 2. Numeric rating scale (NRS) for pain (0−10) at postoperative 1, underwent C-sec, perioperative MgSO4 administration did not 2, 3, and 4 day. The results are expressed as median (horizontal line) reduce postoperative pain [17]. The exact cause of the with 1st and 3rd quartiles (boxes), and 10th and 90th percentiles (vertical conflicting results is unknown, however, the main difference lines). POD: postoperative day. Group N: parturients diagnosed as normal pregnancy. Group P: parturients diagnosed with preeclampsia. from our study was that they used the epidural PCA for postoperative analgesia. Epidural PCA is superior to intravenous PCA for the management of postoperative pain significantly lower pain score on POD 1, 2, and 3. This [18,19], therefore, the analgesic adjuvant effect of MgSO4 finding seems to have more clinical implication considering the might have been masked by the epidural analgesia in their fewer rescue analgesic drugs required after C-sec delivery in results [17]. preeclampsia parturients. To our knowledge, this is the first In previous prospective studies [4,5,20,21], the administered report about the analgesic adjuvant effects of MgSO4 in MgSO4 dose (40−50 mg/kg bolus followed by 8−15 mg/kg/h) obstetric patients with preeclampsia. was sufficient to have an analgesic adjuvant effect at serum
In obstetrics, MgSO4 is well-established as preventing eclam- magnesium concentrations of 1.1−1.4 mmol/L. In this study, ptic seizures in parturients with preeclampsia and recommended the perioperative serum magnesium concentration almost as a tocolytic agent to treat preterm labor [6]. Furthermore, it doubled to 2.1−2.2 mmol/L. Therefore, the increased serum has been suggested as an analgesic adjuvant in surgical pati- magnesium level of group P can be considered the most ents [4,7] and for other chronic pain conditions, including important element that improved postoperative analgesia. neuropathic pain [8], postherpetic neuralgia [9], and dysme- The subjects of this retrospective review were parturients, norrheal [10]. therefore, a specific adverse consequence of MgSO4 was Central sensitization initiation and maintenance involves the observed. The frequency of RBC transfusions was higher in activation of NMDA receptors [11]. Magnesium has no direct preeclampsia patients. It can be assumed that the uterine analgesic properties, however, it acts as an NMDA receptor contraction was not as great, and thereby intraoperative blood antagonist, inhibiting calcium ions from entering cells. loss might be greater in these patients. Because of the 140 Anesth Pain Med Vol. 7, No. 2, 2012
tocolytic effect of MgSO4 [22], the incidence of postpartum evidence that perioperative MgSO4 administration may provide hemorrhage was increased and more oxytocin is required in better postoperative pain control with less rescue analgesic use preeclampsia [23]. However, it was reported that estimated in preeclampsia parturients undergoing C-sec. blood loss during C-sec was comparable whether MgSO4 was administered or not in general parturients [24]. Angiogenic REFERENCES factors in maternal circulation and systemic endothelial dysfunction (proposed pathophysiologic mechanisms of 1. Turner JA. Diagnosis and management of pre-eclampsia: an preeclampsia) were also suggested to be associated with update. Int J Womens Health 2010; 2: 327-37. 2. Ozcan PE, Tugrul S, Senturk NM, Uludag E, Cakar N, Telci L, postpartum bleeding [25]. Therefore, the increased transfusion et al. 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