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A randomized trial of crystalloid versus colloid solution for prevention of hypotension during spinal or low-dose combined spinal-epidural anesthesia for elective cesarean delivery
International Journal of Obstetric Anesthesia (2007) 16, 8–12 Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijoa.2006.07.004
ORIGINAL ARTICLE
A randomized trial of crystalloid versus colloid solution for prevention of hypotension during spinal or low-dose combined spinal-epidural anesthesia for elective cesarean delivery J-S. Ko, C-S. Kim, H-S. Cho, D-H. Choi Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Background: Spinal anesthesia for cesarean delivery is commonly associated with hypotension and nausea and vomiting, and preload with crystalloid or colloid solution is widely recommended. Low-dose spinal via the combined spinal-epidural technique appears to cause less hypotension and nausea and vomiting. The aim of this study was to investigate whether the combined use of colloid preload and combined spinal-epidural technique might further reduce the rates of these symptoms. Methods: Women undergoing elective cesarean delivery were randomly allocated to one of four groups (50 in each) to receive crystalloid preload before spinal anesthesia, colloid preload before spinal anesthesia, crystalloid preload before combined spinal-epidural anesthesia, and colloid preload before combined spinal-epidural anesthesia. The incidences of hypotension and nausea and vomiting were compared. Spinal anesthesia was performed with 0.5% hyperbaric bupivacaine 9 mg and fentanyl 20 lg, and combined spinal-epidural anesthesia with 0.5% hyperbaric bupivacaine 6 mg + fentanyl 20 lg followed by epidural injection of 0.25% bupivacaine 10 mL. Results: The frequencies of hypotension were 44%, 18%, 24%, and 20% in crystalloid preload-spinal anesthesia, colloid preload-spinal anesthesia, crystalloid preload-combined spinal epidural anesthesia, and colloid preload-combined spinal epidural anesthesia groups, respectively. The frequencies of nausea and vomiting were 20%, 2%, 8%, and 4% in respective groups. Conclusion: Colloid preload and low-dose spinal anesthesia alone or in combination lowered the incidences of hypotension and nausea. However, the combination of two methods failed to demonstrate further decreases in the incidence of the symptoms compared to the colloid-spinal anesthesia or crystalloid-combined spinal-epidural anesthesia groups. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Cesarean delivery; Spinal anesthesia; Combined spinal-epidural anesthesia; Preload; Crystalloid; Colloid
including left uterine displacement, vasopressors and volume preload have been tried with some degree of effectiveness. Nonetheless, maternal hypotension and its associated symptoms, nausea and vomiting still persist, despite many efforts to improve their treatment and prevention. Many anesthesiologists have historically recommended rapid administration of crystalloid solutions before spinal anesthesia to reduce hypotension.1–3 However, some have questioned the beneficial effect of crystalloid prehydration and have demonstrated that there is no significant relationship between the amount of crystalloid and the incidence of hypotension.4–7 As an alternative, prehydration with colloid solution has been proposed and demonstrated to be superior in reducing the
INTRODUCTION Hypotension is the most common side effect of spinal anesthesia, and many methods to reduce hypotension Accepted July 2006 Presented at the 24th World Congress of the European Society of Regional Anesthesia & Pain Therapy, Berlin, Germany, 2005. The abstract was published in Reg Anesth Pain Med 2005; 30(5) Suppl 1: p 74. Correspondence to: Dr. Duck Hwan Choi, Department of Anesthesiology and Pain Medicine, Samsung Medical Center, 50 ILwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea. Tel.: +82 2 3410 2466; fax: +82 2 3410 0361. E-mail: [email protected]. 8
Prevention of hypotension for elective cesarean delivery 9 incidence of hypotension by increasing maternal cardiac output and maintaining colloid oncotic pressure.8–10 The combined spinal-epidural (CSE) technique has gained widespread popularity because it provides rapid onset of spinal analgesia with the benefit of epidural anesthesia. More importantly, CSE has allowed the intrathecal dose of local anesthetic to be greatly reduced, thereby potentially reducing associated complications, hypotension and nausea and vomiting.11 Many techniques have been tried to eliminate hypotension, but a recent Cochrane review reported that there is no established ideal technique and suggested future studies should focus on combinations of interventions.12 The aim of this study was to investigate whether the combined use of colloid preload and CSE would produce a further decrease on the incidence of hypotension and nausea and vomiting in parturients.
METHODS After institutional review board approval and written informed consent, a prospective randomized and double-blinded study was performed in 202 women (ASA I-II) with singleton term pregnancy (P38 weeks) scheduled for elective cesarean delivery. All the women were in good health with uncomplicated pregnancies. Excluded were patients with pregnancy-induced hypertension, contraindications to regional anesthesia, and cardiac, renal, or other organ-system disease. Also excluded were patients presenting for emergency delivery and parturients in active labor. The patients were allocated to one of four groups (50 in each group) using a computer-generated randomization list: crystalloid preload-spinal anesthesia (CR-SA), colloid preload-spinal anesthesia (CO-SA), crystalloid preload-combined spinal epidural anesthesia (CR-CSE), and colloid preload-combined spinal epidural anesthesia (CO-CSE). The patients’ ward blood pressures were used as baseline values. On arrival in the operating room, electrocardiogram, non-invasive blood pressure and pulse oximetry were monitored. CR-SA and CR-CSE groups received a rapid infusion of lactated Ringer’s solution 1000-1500 mL (20 mL/kg) warmed to body temperature, and CO-SA and CO-CSE groups were given 6% hydoxyethylstarch (HES: VoluvenÒ, Fresenius Kabi, Germany) 500 mL within 5-10 min before the subarachnoid block. Anesthesiologists were blinded to the types of fluids. Oxygen was administered at a flow rate of 3 L/min through nasal cannulae. With the patient in the right lateral position, a lumbar puncture was performed at the third lumbar interspace (L3-4) using the midline approach. In the CSE group, an 18-gauge Tuohy needle (EspocanÒ; B.Braun, Melsungen, Germany) was introduced using loss of resistance
to air, and the dura was punctured with a 27-gauge Sprotte needle using the needle-through-needle technique. After confirming the subarachnoid space with aspiration of cerebrospinal fluid, 0.5% hyperbaric bupivacaine 6 mg mixed with fentanyl 20 lg was administered. After withdrawal of the spinal needle, a 20-gauge epidural catheter was inserted through the epidural needle 3-4 cm into the epidural space. Patients were then placed in the supine position with left uterine displacement using an airbag under the right hip; 5 min after the intrathecal injection, 0.25% bupivacaine 10 mL was given through the epidural catheter to all patients following the methods from our previous study.13 Patients in the spinal group were given hyperbaric 0.5% bupivacaine 9 mg mixed with fentanyl 20 lg through a 27-gauge Sprotte needle (PencanÒ, B.Braun, Melsungen, Germany) via a 22-gauge introducer after free flow of cerebrospinal fluid was observed. A sham epidural catheter as used in the CSE group was applied to the patient’s back, and immediately after this, patients were turned supine with left uterine displacement. Five minutes after the intrathecal injection, 0.25% bupivacaine 10 mL was administered into the sham catheter and was soaked up by gauze on the patient’s back away from the puncture wound. Completion of the intrathecal injection was taken as time 0 min in both groups. The investigator, who was not aware of the anesthetic technique allocated to each patient, entered the operating room immediately after the catheter had been secured and recorded all variables. Maternal blood pressure was recorded every minute for 10 min after the intrathecal injection, at 2-min intervals for the next 10 min and at 5-min intervals thereafter. Hypotension was defined as a 20% or more decrease from the baseline level or systolic pressure below 95 mmHg, and was treated immediately with ephedrine 5 mg i.v. repeated whenever necessary. Sensory block was tested 5, 10, 15, 20, 30, 60, 90 and 120 min after induction. Sensory levels were checked by pin-prick using a 25-gauge Whitacre needle. Intraoperative pain, >30 mm on the visual analogue scale (VAS) of 0-100 mm, was to be treated with fentanyl 50 lg i.v. once or twice. Patients not responding to two fentanyl injections were to be excluded from this study because it would be necessary to violate the blinding in order to treat the CSE group by local anesthetic injection through the epidural catheter and the spinal group by nitrous oxide and/ or inhalation of sevoflurane. Adverse effects such as nausea and vomiting, shivering, pruritus and dizziness after induction of anesthesia were checked every 10 min throughout the operation. The times required for sensory recovery to T10 and the onset of postoperative pain were recorded in the post anesthetic care unit. Prospective power analysis based on data from previous pilot studies in our department showed that
10 International Journal of Obstetric Anesthesia There were no significant differences between the groups in maximum block heights or the incidences of adverse effects (Table 2). Sensory block was adequate in all four groups 10 min after the intrathecal injection (median upper sensory level: T4). The median upper sensory level 30 min after the intrathecal injection of anesthetics was T3 in all groups and no parturients complained of intraoperative pain. The colloid groups showed significantly lower incidence of hypotension than CR-SA group (CR-SA vs. CO-SA: P = 0.023; CR-SA vs. CO-CSE: P = 0.047). However, there was no significant difference between the two colloid groups. The colloid and CSE groups tended to have lower ephedrine requirements but this failed to reach statistical significance. The incidences of nausea and vomiting were significantly lower in the colloid and CSE groups (P = 0.0102) compared to the CR-SA group. There was no significant difference between the colloid groups.
50 patients per group would give more than 80% power with a of 0.05 to detect a 25% difference in the incidences of hypotension between the two groups. For statistical analysis, patient’s characteristics, sensory block variables, operation time, amount of hydration and ephedrine doses among the four groups were compared using oneway ANOVA followed by Tukey’s method for multiple comparisons. The differences among the four groups in incidences of adverse effects such as hypotension, pain, nausea and vomiting were analyzed by v2 test or Fisher’s exact test, and differences of the above variables in any two groups were analyzed using Fisher’s exact test using permutation method for multiple testing. P < 0.05 was considered to be statistically significant.
RESULTS Fifty patients were randomly assigned to the CR-CSE group but two patients were excluded, one because of failed spinal block and the other because of later identified intravenous placement of the epidural catheter and two further patients were recruited as replacements. There were no significant differences among the four groups with regard to age, weight, height, and duration of operation (skin-to-skin). The total amounts of preload volumes (LR or LR + HES) infused were similar among the groups (Table 1).
DISCUSSION In this present study, colloid preload significantly reduced the incidence of hypotension and nausea compared to crystalloid preload in the SA groups. However, low-dose spinal using the CSE technique in combination with colloid preload failed to show a further decrease in the incidence of symptoms.
Table 1. Patient characteristics CR-SA (n = 50)
CO-SA (n = 50)
CR-CSE (n = 50)
CO-CSE (n = 50)
Age (years) Weight (kg) Height (cm)
31.9 € 3.6 69.4 € 9.5 160 € 5.3
31.7 € 3.0 67.6 € 7.5 159 € 4.5
30.7 € 3.5 68.3 € 7.2 160 € 4.6
33.1 € 3.9 68.9 € 10.2 159 € 5.0
Preload (mL) colloid crystalloid total Duration of operation (min)
0 1280 € 266 1280 € 266 51.5 € 14.6
500 763 € 215 1263 € 215 56.0 € 17.2
0 1272 € 278 1272 € 278 50.3 € 18.1
500 801 € 296 1301 € 296 53.8 € 16.3
Values are mean € SD. No significant difference among the groups except preload volume. CR-SA = crystalloid preload-spinal anesthesia group; CO-SA = colloid preload-spinal anesthesia group; CR-CSE = crystalloid preload-combined spinal epidural anesthesia group; CO-CSE = colloid preload-combined spinal epidural anesthesia group.
Table 2. Maximum block heights and incidences of adverse effects
Sensory level Pain/discomfort Hypotension Ephedrine (mg) Nausea & vomiting
CR-SA (n = 50)
CO-SA (n = 50)
CR-CSE (n = 50)
CO-CSE (n = 50)
T3 (C6-T5) 0/0 22 (44%)* 10 (5-20) 10 (20%)*
T3 (T1-T6) 0/1 9 (18%) 7.5 (5-20) 1 (2%)
T3 (T1-T6) 0/1 12 (24%) 5 (5-15) 4 (8%)
T3 (C8-T5) 0/0 10 (20%) 5 (5-15) 2 (4%)
P NS NS 0.012 NS 0.006
Values are sensory block segment heights (range) or numbers (percent). CR-SA = crystalloid preload-spinal anesthesia group; CO-SA = colloid preload-spinal anesthesia group; CR-CSE = crystalloid preload-combined spinal epidural anesthesia group; CO-CSE = colloid preload-combined spinal epidural anesthesia group. NS: not significant. * P < 0.05 = Significantly different from CO-SA, CR-CSE and CO-CSE.
Prevention of hypotension for elective cesarean delivery 11 The efficacy of prehydration has been studied extensively in the prevention of hypotension following spinal anesthesia for cesarean delivery, but the optimum types and doses of preload solutions remain controversial. Since the concept of prehydration was introduced into clinical practice by Marx and Wollman in 1968, fluid loading with crystalloid before spinal anesthesia has been common practice.2,3 However, several recent investigations have demonstrated that crystalloid preload does not decrease the incidence or severity of hypotension.6,14 Furthermore, a large volume of crystalloid preloading in parturients may lead to numerous unwanted side-effects such as severe dilutional anemia resulting in decreased oxygen transport capacity, decreased colloid oncotic pressure, pulmonary edema and increased central venous pressure up to clinically unacceptable values.7,15,16 Alternatively, colloid solutions have been shown, with little doubt, to decrease the incidence of hypotension when infused before spinal anesthesia for cesarean delivery.16–18 Dahlgren et al. demonstrated the efficacy of colloid compared to crystalloid hydration and concluded that the protective effect of the colloid solution increased with increased severity of hypotension.8 In line with the above studies, our results showed that the incidences of hypotension and associated nausea and vomiting were significantly lower in the colloid than in the crystalloid groups. Typically, 12-15 mg of bupivacaine has been recommended for intrathecal block for cesarean delivery to prevent visceral pain and to ensure an adequate sensory block level and duration.19 However, numerous recent studies have reported that a combination of opioids and local anesthetics permits the local anesthetic dose to be significantly reduced.20,21 The combined spinalepidural technique has gained increasing popularity because of its selected advantages of both spinal and epidural anesthesia.22 It provides the rapid onset and dense block of spinal analgesia, and combined epidural injection functions as a back-up for an inadequate spinal surgical block and even offers extended duration of epidural anesthesia.23 Our previous study of CSE anesthesia demonstrated that a lower spinal dose elevated the sensory block level more slowly, and hypotension and nausea occurred less frequently resulting in better hemodynamic stability than single-shot spinal anesthesia for cesarean delivery.13 Similarly, Ben-David et al. reported that this reduced intrathecal anesthetic requirement decreased the intensity and duration of sympathetic and motor blockade, and thus, lessened the severity of maternal hypotension.24 In agreement with these studies, the results of our current study showed that the incidences of hypotension, nausea and vomiting in the CSE group using 0.5% bupivacaine 6 mg + fentanyl 20 lg were significantly lower than in the SA group. As suggested by the recent Cochrane review, a combination of techniques was used to prevent spinal-induced
hypotension for cesarean delivery in studies by Vercauteran et al. and Ngan Kee et al.17,25 Vercauteren et al. reported that a low-dose spinal anesthetic combined with a 10% hydroxyethylstarch (HES) preload and appropriate vasopressor administration significantly reduced the incidence of hypotension.25 Similarly, in the study by Ngan Kee et al., hypotension was virtually eliminated with the combination of a high-dose a-agonist vasoconstrictor (phenylephrine) and rapid crystalloid cohydration.17 In our previous study we demonstrated the efficacy of low-dose spinal anesthesia13 and in this study, we expected the combination of colloid prehydration would have an added effect in the prevention of maternal hypotension. However, the combination of two methods failed to show a further decrease in the incidence of hypotension compared to each individual method. This result may be attributed to the use of low-dose (9 mg) spinal anesthesia even in the spinal anesthesia groups leading to a lower incidence and severity of hypotension and nausea, and thus, the colloid preload alone may have provided a sufficient preventive effect. In addition, our study showed that hypotension was readily corrected by the administration of a small dose of ephedrine, if needed, perhaps due to the reduced severity of hypotension. Therefore, routine administration of vasopressors as tried in other studies seems unnecessary. Despite the advantages of colloid preload, many have voiced concern over cost and, more importantly, the risk of anaphylaxis.8,26,27 Dahlgren et al. argued that the modest reduction in incidence of hypotension does not justify the use of an expensive colloid with a possible risk for adverse reactions such as anaphylaxis.8 Therefore, colloid should perhaps be reserved for cases with expected severe hypotension. Moreover, as our study revealed that the crystalloid preloading with low-dose spinal anesthesia using the CSE technique showed a low incidence of hypotension, the routine preventive colloid preload seems largely unnecessary. The limitations of our study were that we did not measure the degree or intensity of the symptoms such as heart rate and blood pressure changes, timing of hypotension, and intensity of nausea and vomiting, and we did not include a group with no preload. Moreover, if the epidural solution had not been given routinely, a true low-dose spinal might have been provided yielding greater differences between the groups. Additionally, we did not collect data on neonatal outcomes such as Apgar scores or cord blood gases. Future studies taking account of these issues might be needed. In conclusion, colloid preload and low-dose spinal anesthesia alone or in combination reduced the incidences of hypotension and nausea. However, the combination of two methods failed to demonstrate further decreases in the incidence of the symptoms compared to the colloid-SA or crystalloid-CSE groups.
12 International Journal of Obstetric Anesthesia REFERENCES 1. Clark R B, Thompson D S, Thompson C H. Prevention of spinal hypotension associated with Cesarean section. Anesthesiology 1976; 45: 670–4. 2. Marx G F, Cosmi E V, Wollman S B. Biochemical status and clinical condition of mother and infant at cesarean section. Anesth Analg 1969; 48: 986–94. 3. Wollman S B, Marx G F. Acute hydration for prevention of hypotension of spinal anesthesia in parturients. Anesthesiology 1968; 29: 374–80. 4. Jackson R, Reid J A, Thorburn J. Volume preloading is not essential to prevent spinal-induced hypotension at caesarean section. Br J Anaesth 1995; 75: 262–5. 5. Park G E, Hauch M A, Curlin F, et al. The effects of varying volumes of crystalloid administration before cesarean delivery on maternal hemodynamics and colloid osmotic pressure. Anesth Analg 1996; 83: 299–303. 6. Rout C C, Akoojee S S, Rocke D A, Gouws E. Rapid administration of crystalloid preload does not decrease the incidence of hypotension after spinal anaesthesia for elective caesarean section. Br J Anaesth 1992; 68: 394–7. 7. Rout C C, Rocke D A, Levin J, et al. A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal anesthesia for elective cesarean section. Anesthesiology 1993; 79: 262–9. 8. Dahlgren G, Granath F, Pregner K, et al. Colloid vs. crystalloid preloading to prevent maternal hypotension during spinal anesthesia for elective cesarean section. Acta Anaesthesiol Scand 2005; 49: 1200–6. 9. Siddik S M, Aouad M T, Kai G E, et al. Hydroxyethylstarch 10% is superior to Ringer’s solution for preloading before spinal anesthesia for Cesarean section. Can J Anaesth 2000; 47: 616–21. 10. Ueyama H, He Y L, Tanigami H, et al. Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal anesthesia for elective Cesarean section. Anesthesiology 1999; 91: 1571–6. 11. Rawal N, Van Zundert A, Holmstrom B, Crowhurst J A. Combined spinal-epidural technique. Reg Anesth 1997; 22: 406–23. 12. Emmett RS, Cyna AM, Andrew M, Simmons SW. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev 2002: CD002251. 13. Choi D H, Ahn H J, Kim J A. Combined low-dose spinal-epidural anesthesia versus single-shot spinal anesthesia for elective cesarean delivery. Int J Obstet Anesth 2006; 15: 13–7.
14. Rout C, Rocke D A. Spinal hypotension associated with Cesarean section: will preload ever work? Anesthesiology 1999; 91: 1565–7. 15. MacLennan F M, MacDonald A F, Campbell D M. Lung water during the puerperium. Anaesthesia 1987; 42: 141–7. 16. French G W, White J B, Howell S J, Popat M. Comparison of pentastarch and Hartmann’s solution for volume preloading in spinal anaesthesia for elective caesarean section. Br J Anaesth 1999; 83: 475–7. 17. Ngan Kee W D, Khaw K S, Ng F F. Prevention of hypotension during spinal anesthesia for cesarean delivery: an effective technique using combination phenylephrine infusion and crystalloid cohydration. Anesthesiology 2005; 103: 744–50. 18. Riley E T, Cohen S E, Rubenstein A J, Flanagan B. Prevention of hypotension after spinal anesthesia for cesarean section: six percent hetastarch versus lactated Ringer’s solution. Anesth Analg 1995; 81: 838–42. 19. Finucane B T. Spinal anesthesia for cesarean delivery. The dosage dilemma. Reg Anesth 1995; 20: 87–9. 20. Ben-David B, Solomon E, Levin H, et al. Intrathecal fentanyl with small-dose dilute bupivacaine: better anesthesia without prolonging recovery. Anesth Analg 1997; 85: 560–5. 21. Choi D H, Ahn H J, Kim M H. Bupivacaine-sparing effect of fentanyl in spinal anesthesia for cesarean delivery. Reg Anesth Pain Med 2000; 25: 240–5. 22. Rawal N, Holmstrom B, Crowhurst J A, Van Zundert A. The combined spinal-epidural technique. Anesthesiol Clin North America 2000; 18: 267–95. 23. Rawal N, Schollin J, Wesstrom G. Epidural versus combined spinal epidural block for cesarean section. Acta Anaesthesiol Scand 1988; 32: 61–6. 24. Ben-David B, Miller G, Gavriel R, Gurevitch A. Low-dose bupivacaine-fentanyl spinal anesthesia for cesarean delivery. Reg Anesth Pain Med 2000; 25: 235–9. 25. Vercauteren M P, Coppejans H C, Hoffmann V H, et al. Prevention of hypotension by a single 5-mg dose of ephedrine during small-dose spinal anesthesia in prehydrated cesarean delivery patients. Anesth Analg 2000; 90: 324–7. 26. Cullen M J, Singer M. Severe anaphylactoid reaction to hydroxyethyl starch. Anaesthesia 1990; 45: 1041–2. 27. Fisher M M, Brady P W. Adverse reactions to plasma volume expanders. Drug Saf 1990; 5: 86–93.
ORIGINAL ARTICLE
A randomized trial of crystalloid versus colloid solution for prevention of hypotension during spinal or low-dose combined spinal-epidural anesthesia for elective cesarean delivery J-S. Ko, C-S. Kim, H-S. Cho, D-H. Choi Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Background: Spinal anesthesia for cesarean delivery is commonly associated with hypotension and nausea and vomiting, and preload with crystalloid or colloid solution is widely recommended. Low-dose spinal via the combined spinal-epidural technique appears to cause less hypotension and nausea and vomiting. The aim of this study was to investigate whether the combined use of colloid preload and combined spinal-epidural technique might further reduce the rates of these symptoms. Methods: Women undergoing elective cesarean delivery were randomly allocated to one of four groups (50 in each) to receive crystalloid preload before spinal anesthesia, colloid preload before spinal anesthesia, crystalloid preload before combined spinal-epidural anesthesia, and colloid preload before combined spinal-epidural anesthesia. The incidences of hypotension and nausea and vomiting were compared. Spinal anesthesia was performed with 0.5% hyperbaric bupivacaine 9 mg and fentanyl 20 lg, and combined spinal-epidural anesthesia with 0.5% hyperbaric bupivacaine 6 mg + fentanyl 20 lg followed by epidural injection of 0.25% bupivacaine 10 mL. Results: The frequencies of hypotension were 44%, 18%, 24%, and 20% in crystalloid preload-spinal anesthesia, colloid preload-spinal anesthesia, crystalloid preload-combined spinal epidural anesthesia, and colloid preload-combined spinal epidural anesthesia groups, respectively. The frequencies of nausea and vomiting were 20%, 2%, 8%, and 4% in respective groups. Conclusion: Colloid preload and low-dose spinal anesthesia alone or in combination lowered the incidences of hypotension and nausea. However, the combination of two methods failed to demonstrate further decreases in the incidence of the symptoms compared to the colloid-spinal anesthesia or crystalloid-combined spinal-epidural anesthesia groups. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Cesarean delivery; Spinal anesthesia; Combined spinal-epidural anesthesia; Preload; Crystalloid; Colloid
including left uterine displacement, vasopressors and volume preload have been tried with some degree of effectiveness. Nonetheless, maternal hypotension and its associated symptoms, nausea and vomiting still persist, despite many efforts to improve their treatment and prevention. Many anesthesiologists have historically recommended rapid administration of crystalloid solutions before spinal anesthesia to reduce hypotension.1–3 However, some have questioned the beneficial effect of crystalloid prehydration and have demonstrated that there is no significant relationship between the amount of crystalloid and the incidence of hypotension.4–7 As an alternative, prehydration with colloid solution has been proposed and demonstrated to be superior in reducing the
INTRODUCTION Hypotension is the most common side effect of spinal anesthesia, and many methods to reduce hypotension Accepted July 2006 Presented at the 24th World Congress of the European Society of Regional Anesthesia & Pain Therapy, Berlin, Germany, 2005. The abstract was published in Reg Anesth Pain Med 2005; 30(5) Suppl 1: p 74. Correspondence to: Dr. Duck Hwan Choi, Department of Anesthesiology and Pain Medicine, Samsung Medical Center, 50 ILwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea. Tel.: +82 2 3410 2466; fax: +82 2 3410 0361. E-mail: [email protected]. 8
Prevention of hypotension for elective cesarean delivery 9 incidence of hypotension by increasing maternal cardiac output and maintaining colloid oncotic pressure.8–10 The combined spinal-epidural (CSE) technique has gained widespread popularity because it provides rapid onset of spinal analgesia with the benefit of epidural anesthesia. More importantly, CSE has allowed the intrathecal dose of local anesthetic to be greatly reduced, thereby potentially reducing associated complications, hypotension and nausea and vomiting.11 Many techniques have been tried to eliminate hypotension, but a recent Cochrane review reported that there is no established ideal technique and suggested future studies should focus on combinations of interventions.12 The aim of this study was to investigate whether the combined use of colloid preload and CSE would produce a further decrease on the incidence of hypotension and nausea and vomiting in parturients.
METHODS After institutional review board approval and written informed consent, a prospective randomized and double-blinded study was performed in 202 women (ASA I-II) with singleton term pregnancy (P38 weeks) scheduled for elective cesarean delivery. All the women were in good health with uncomplicated pregnancies. Excluded were patients with pregnancy-induced hypertension, contraindications to regional anesthesia, and cardiac, renal, or other organ-system disease. Also excluded were patients presenting for emergency delivery and parturients in active labor. The patients were allocated to one of four groups (50 in each group) using a computer-generated randomization list: crystalloid preload-spinal anesthesia (CR-SA), colloid preload-spinal anesthesia (CO-SA), crystalloid preload-combined spinal epidural anesthesia (CR-CSE), and colloid preload-combined spinal epidural anesthesia (CO-CSE). The patients’ ward blood pressures were used as baseline values. On arrival in the operating room, electrocardiogram, non-invasive blood pressure and pulse oximetry were monitored. CR-SA and CR-CSE groups received a rapid infusion of lactated Ringer’s solution 1000-1500 mL (20 mL/kg) warmed to body temperature, and CO-SA and CO-CSE groups were given 6% hydoxyethylstarch (HES: VoluvenÒ, Fresenius Kabi, Germany) 500 mL within 5-10 min before the subarachnoid block. Anesthesiologists were blinded to the types of fluids. Oxygen was administered at a flow rate of 3 L/min through nasal cannulae. With the patient in the right lateral position, a lumbar puncture was performed at the third lumbar interspace (L3-4) using the midline approach. In the CSE group, an 18-gauge Tuohy needle (EspocanÒ; B.Braun, Melsungen, Germany) was introduced using loss of resistance
to air, and the dura was punctured with a 27-gauge Sprotte needle using the needle-through-needle technique. After confirming the subarachnoid space with aspiration of cerebrospinal fluid, 0.5% hyperbaric bupivacaine 6 mg mixed with fentanyl 20 lg was administered. After withdrawal of the spinal needle, a 20-gauge epidural catheter was inserted through the epidural needle 3-4 cm into the epidural space. Patients were then placed in the supine position with left uterine displacement using an airbag under the right hip; 5 min after the intrathecal injection, 0.25% bupivacaine 10 mL was given through the epidural catheter to all patients following the methods from our previous study.13 Patients in the spinal group were given hyperbaric 0.5% bupivacaine 9 mg mixed with fentanyl 20 lg through a 27-gauge Sprotte needle (PencanÒ, B.Braun, Melsungen, Germany) via a 22-gauge introducer after free flow of cerebrospinal fluid was observed. A sham epidural catheter as used in the CSE group was applied to the patient’s back, and immediately after this, patients were turned supine with left uterine displacement. Five minutes after the intrathecal injection, 0.25% bupivacaine 10 mL was administered into the sham catheter and was soaked up by gauze on the patient’s back away from the puncture wound. Completion of the intrathecal injection was taken as time 0 min in both groups. The investigator, who was not aware of the anesthetic technique allocated to each patient, entered the operating room immediately after the catheter had been secured and recorded all variables. Maternal blood pressure was recorded every minute for 10 min after the intrathecal injection, at 2-min intervals for the next 10 min and at 5-min intervals thereafter. Hypotension was defined as a 20% or more decrease from the baseline level or systolic pressure below 95 mmHg, and was treated immediately with ephedrine 5 mg i.v. repeated whenever necessary. Sensory block was tested 5, 10, 15, 20, 30, 60, 90 and 120 min after induction. Sensory levels were checked by pin-prick using a 25-gauge Whitacre needle. Intraoperative pain, >30 mm on the visual analogue scale (VAS) of 0-100 mm, was to be treated with fentanyl 50 lg i.v. once or twice. Patients not responding to two fentanyl injections were to be excluded from this study because it would be necessary to violate the blinding in order to treat the CSE group by local anesthetic injection through the epidural catheter and the spinal group by nitrous oxide and/ or inhalation of sevoflurane. Adverse effects such as nausea and vomiting, shivering, pruritus and dizziness after induction of anesthesia were checked every 10 min throughout the operation. The times required for sensory recovery to T10 and the onset of postoperative pain were recorded in the post anesthetic care unit. Prospective power analysis based on data from previous pilot studies in our department showed that
10 International Journal of Obstetric Anesthesia There were no significant differences between the groups in maximum block heights or the incidences of adverse effects (Table 2). Sensory block was adequate in all four groups 10 min after the intrathecal injection (median upper sensory level: T4). The median upper sensory level 30 min after the intrathecal injection of anesthetics was T3 in all groups and no parturients complained of intraoperative pain. The colloid groups showed significantly lower incidence of hypotension than CR-SA group (CR-SA vs. CO-SA: P = 0.023; CR-SA vs. CO-CSE: P = 0.047). However, there was no significant difference between the two colloid groups. The colloid and CSE groups tended to have lower ephedrine requirements but this failed to reach statistical significance. The incidences of nausea and vomiting were significantly lower in the colloid and CSE groups (P = 0.0102) compared to the CR-SA group. There was no significant difference between the colloid groups.
50 patients per group would give more than 80% power with a of 0.05 to detect a 25% difference in the incidences of hypotension between the two groups. For statistical analysis, patient’s characteristics, sensory block variables, operation time, amount of hydration and ephedrine doses among the four groups were compared using oneway ANOVA followed by Tukey’s method for multiple comparisons. The differences among the four groups in incidences of adverse effects such as hypotension, pain, nausea and vomiting were analyzed by v2 test or Fisher’s exact test, and differences of the above variables in any two groups were analyzed using Fisher’s exact test using permutation method for multiple testing. P < 0.05 was considered to be statistically significant.
RESULTS Fifty patients were randomly assigned to the CR-CSE group but two patients were excluded, one because of failed spinal block and the other because of later identified intravenous placement of the epidural catheter and two further patients were recruited as replacements. There were no significant differences among the four groups with regard to age, weight, height, and duration of operation (skin-to-skin). The total amounts of preload volumes (LR or LR + HES) infused were similar among the groups (Table 1).
DISCUSSION In this present study, colloid preload significantly reduced the incidence of hypotension and nausea compared to crystalloid preload in the SA groups. However, low-dose spinal using the CSE technique in combination with colloid preload failed to show a further decrease in the incidence of symptoms.
Table 1. Patient characteristics CR-SA (n = 50)
CO-SA (n = 50)
CR-CSE (n = 50)
CO-CSE (n = 50)
Age (years) Weight (kg) Height (cm)
31.9 € 3.6 69.4 € 9.5 160 € 5.3
31.7 € 3.0 67.6 € 7.5 159 € 4.5
30.7 € 3.5 68.3 € 7.2 160 € 4.6
33.1 € 3.9 68.9 € 10.2 159 € 5.0
Preload (mL) colloid crystalloid total Duration of operation (min)
0 1280 € 266 1280 € 266 51.5 € 14.6
500 763 € 215 1263 € 215 56.0 € 17.2
0 1272 € 278 1272 € 278 50.3 € 18.1
500 801 € 296 1301 € 296 53.8 € 16.3
Values are mean € SD. No significant difference among the groups except preload volume. CR-SA = crystalloid preload-spinal anesthesia group; CO-SA = colloid preload-spinal anesthesia group; CR-CSE = crystalloid preload-combined spinal epidural anesthesia group; CO-CSE = colloid preload-combined spinal epidural anesthesia group.
Table 2. Maximum block heights and incidences of adverse effects
Sensory level Pain/discomfort Hypotension Ephedrine (mg) Nausea & vomiting
CR-SA (n = 50)
CO-SA (n = 50)
CR-CSE (n = 50)
CO-CSE (n = 50)
T3 (C6-T5) 0/0 22 (44%)* 10 (5-20) 10 (20%)*
T3 (T1-T6) 0/1 9 (18%) 7.5 (5-20) 1 (2%)
T3 (T1-T6) 0/1 12 (24%) 5 (5-15) 4 (8%)
T3 (C8-T5) 0/0 10 (20%) 5 (5-15) 2 (4%)
P NS NS 0.012 NS 0.006
Values are sensory block segment heights (range) or numbers (percent). CR-SA = crystalloid preload-spinal anesthesia group; CO-SA = colloid preload-spinal anesthesia group; CR-CSE = crystalloid preload-combined spinal epidural anesthesia group; CO-CSE = colloid preload-combined spinal epidural anesthesia group. NS: not significant. * P < 0.05 = Significantly different from CO-SA, CR-CSE and CO-CSE.
Prevention of hypotension for elective cesarean delivery 11 The efficacy of prehydration has been studied extensively in the prevention of hypotension following spinal anesthesia for cesarean delivery, but the optimum types and doses of preload solutions remain controversial. Since the concept of prehydration was introduced into clinical practice by Marx and Wollman in 1968, fluid loading with crystalloid before spinal anesthesia has been common practice.2,3 However, several recent investigations have demonstrated that crystalloid preload does not decrease the incidence or severity of hypotension.6,14 Furthermore, a large volume of crystalloid preloading in parturients may lead to numerous unwanted side-effects such as severe dilutional anemia resulting in decreased oxygen transport capacity, decreased colloid oncotic pressure, pulmonary edema and increased central venous pressure up to clinically unacceptable values.7,15,16 Alternatively, colloid solutions have been shown, with little doubt, to decrease the incidence of hypotension when infused before spinal anesthesia for cesarean delivery.16–18 Dahlgren et al. demonstrated the efficacy of colloid compared to crystalloid hydration and concluded that the protective effect of the colloid solution increased with increased severity of hypotension.8 In line with the above studies, our results showed that the incidences of hypotension and associated nausea and vomiting were significantly lower in the colloid than in the crystalloid groups. Typically, 12-15 mg of bupivacaine has been recommended for intrathecal block for cesarean delivery to prevent visceral pain and to ensure an adequate sensory block level and duration.19 However, numerous recent studies have reported that a combination of opioids and local anesthetics permits the local anesthetic dose to be significantly reduced.20,21 The combined spinalepidural technique has gained increasing popularity because of its selected advantages of both spinal and epidural anesthesia.22 It provides the rapid onset and dense block of spinal analgesia, and combined epidural injection functions as a back-up for an inadequate spinal surgical block and even offers extended duration of epidural anesthesia.23 Our previous study of CSE anesthesia demonstrated that a lower spinal dose elevated the sensory block level more slowly, and hypotension and nausea occurred less frequently resulting in better hemodynamic stability than single-shot spinal anesthesia for cesarean delivery.13 Similarly, Ben-David et al. reported that this reduced intrathecal anesthetic requirement decreased the intensity and duration of sympathetic and motor blockade, and thus, lessened the severity of maternal hypotension.24 In agreement with these studies, the results of our current study showed that the incidences of hypotension, nausea and vomiting in the CSE group using 0.5% bupivacaine 6 mg + fentanyl 20 lg were significantly lower than in the SA group. As suggested by the recent Cochrane review, a combination of techniques was used to prevent spinal-induced
hypotension for cesarean delivery in studies by Vercauteran et al. and Ngan Kee et al.17,25 Vercauteren et al. reported that a low-dose spinal anesthetic combined with a 10% hydroxyethylstarch (HES) preload and appropriate vasopressor administration significantly reduced the incidence of hypotension.25 Similarly, in the study by Ngan Kee et al., hypotension was virtually eliminated with the combination of a high-dose a-agonist vasoconstrictor (phenylephrine) and rapid crystalloid cohydration.17 In our previous study we demonstrated the efficacy of low-dose spinal anesthesia13 and in this study, we expected the combination of colloid prehydration would have an added effect in the prevention of maternal hypotension. However, the combination of two methods failed to show a further decrease in the incidence of hypotension compared to each individual method. This result may be attributed to the use of low-dose (9 mg) spinal anesthesia even in the spinal anesthesia groups leading to a lower incidence and severity of hypotension and nausea, and thus, the colloid preload alone may have provided a sufficient preventive effect. In addition, our study showed that hypotension was readily corrected by the administration of a small dose of ephedrine, if needed, perhaps due to the reduced severity of hypotension. Therefore, routine administration of vasopressors as tried in other studies seems unnecessary. Despite the advantages of colloid preload, many have voiced concern over cost and, more importantly, the risk of anaphylaxis.8,26,27 Dahlgren et al. argued that the modest reduction in incidence of hypotension does not justify the use of an expensive colloid with a possible risk for adverse reactions such as anaphylaxis.8 Therefore, colloid should perhaps be reserved for cases with expected severe hypotension. Moreover, as our study revealed that the crystalloid preloading with low-dose spinal anesthesia using the CSE technique showed a low incidence of hypotension, the routine preventive colloid preload seems largely unnecessary. The limitations of our study were that we did not measure the degree or intensity of the symptoms such as heart rate and blood pressure changes, timing of hypotension, and intensity of nausea and vomiting, and we did not include a group with no preload. Moreover, if the epidural solution had not been given routinely, a true low-dose spinal might have been provided yielding greater differences between the groups. Additionally, we did not collect data on neonatal outcomes such as Apgar scores or cord blood gases. Future studies taking account of these issues might be needed. In conclusion, colloid preload and low-dose spinal anesthesia alone or in combination reduced the incidences of hypotension and nausea. However, the combination of two methods failed to demonstrate further decreases in the incidence of the symptoms compared to the colloid-SA or crystalloid-CSE groups.
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