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Update on volume therapy in obstetrics
Best Practice & Research Clinical Anaesthesiology 28 (2014) 297e303
Contents lists available at ScienceDirect
Best Practice & Research Clinical Anaesthesiology journal homepage: www.elsevier.com/locate/bean
9
Update on volume therapy in obstetrics Wendy H.L. Teoh, MBBS, FANZCA, FAMS, Senior Consultant, Adj. Assistant Professor a, b, *, Martin Westphal, MD, PhD, Professor, Chief Medical Officer c, d, Tim G. Kampmeier, MD, Research Fellow c a
Department of Women's Anaesthesia, KK Women's and Children's Hospital, Singapore Duke University e NUS Graduate Medical School, Singapore c Department of Anaesthesiology, Pain Medicine and Intensive Care, University Hospital of Muenster, Muenster, Germany d Fresenius Kabi AG, Bad Homburg, Germany b
Keywords: hypotension spinal anaesthesia caesarean delivery preload coload crystalloids colloids HES volume obstetrics
Symptomatic hypotension (maternal nausea, vomiting, dizziness and dyspnoea) during spinal anaesthesia for caesarean delivery remains a prevalent clinical problem. Severe and sustained hypotension can lead to impairment of uteroplacental perfusion, foetal hypoxia, acidosis, neonatal depression and further adverse maternal outcomes of unconsciousness, pulmonary aspiration, apnoea and cardiac arrest. Mechanical methods aimed at countering the effects of aortocaval compression do not reliably prevent maternal hypotension. Intravenous crystalloid preloading (given prior to administration of spinal anaesthesia) has poor efficacy, and focus has changed towards decreased use of crystalloid preload and ephedrine, to increased use of coload (given at the time of spinal administration) with colloids or crystalloids, and early use of phenylephrine. The recent multicentre, randomised, doubleblinded CAESAR trial demonstrated the efficacy of a mixed 500 ml 6% hydroxyethyl starch (HES) 130/0.4 þ 500 ml Ringer's lactate (RL) preload in significantly reducing hypotension, compared to a 1-l RL preload, without adverse effects on coagulation and neonatal outcomes in healthy parturients undergoing caesarean delivery under spinal anaesthesia. © 2014 Elsevier Ltd. All rights reserved.
* Corresponding author. Department of Women's Anaesthesia, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore. Tel.: þ65 81217986; Fax: þ65 62912661. E-mail addresses: [email protected] (W.H.L. Teoh), [email protected] (M. Westphal), tim.kampmeier@ gmail.com (T.G. Kampmeier).
http://dx.doi.org/10.1016/j.bpa.2014.07.004 1521-6896/© 2014 Elsevier Ltd. All rights reserved.
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Introduction In contemporary obstetric anaesthesia practice, neuraxial techniques are the preferred method for providing anaesthesia for caesarean delivery over a general anaesthetic. Compared to an epidural or combined spinaleepidural (CSE), single-shot spinal anaesthesia is most commonly employed as it is easy to perform and provides rapid-onset dense neuroblockade [1,2]. The goal for adequate surgical anaesthesia is a sensory blockade to the T5 dermatome. This is typically achieved by administration of intrathecal hyperbaric bupivacaine ranging from 10 to 12 mg with an opioid adjuvant [3]. All neuraxial techniques are associated with hypotension from the resulting sympathetic blockade. In an effort to alleviate this, the administration of fluids and vasopressors remains the cornerstone of treatment of spinal-induced hypotension, in tandem with avoidance of aortocaval compression by effecting left lateral uterine displacement and use of calf compressors to aid venous return. As the mass of local anaesthetic influences the spread of the block and causes hypotension, lower doses of 4.5e6.6 mg bupivacaine [4e6] as part of a single-shot spinal technique have previously been used for caesarean delivery, but this has raised safety concerns of whether lower doses should be used just because they can be used, due to the potential for unnecessary conversion to general anaesthesia. Lower spinal doses of local anaesthetics, however, can safely be utilised as part of a CSE technique especially if it is imperative to maintain stable intraoperative haemodynamics (e.g., severe preeclamptics and high-risk parturients with cardiac problems) as the epidural catheter allows analgesia supplementation in the event of prolonged surgical duration and breakthrough pain [7,8]. Incidence and physiology of maternal hypotension revisited Hypotension is arbitrarily defined in the literature as a systolic blood pressure <100 mmHg or <80% of the baseline value [9], and is a common sequela after spinal anaesthesia in 55e90% of parturients [10]. Reductions in blood pressure of >30% baseline have also been described in nearly 50% of women undergoing spinal anaesthesia [11]. The risk factors for hypotension include increased sympathetic tone, increasing age, obesity, higher blocks and higher birth weight, but not multiple gestation [12]. The clinical signs of spinal hypotension are usually limited to nausea/vomiting and/or dyspnoea. However, hypotension when severe and sustained can lead to impairment of uteroplacental perfusion (as the vessels are maximally dilated, of low resistance and exhibit no autoregulation), resulting in foetal hypoxia, acidosis, neonatal depression or injury [13] and adverse maternal outcomes of unconsciousness, pulmonary aspiration, apnoea and cardiac arrest. It was traditionally taught that hypotension occurred as a result of decrease in venous return and cardiac output after a spinal anaesthetic. Strategies to increase venous return (leg lifting and mechanical compression of the lower extremities) and aggressive intravascular volume loading have proven largely ineffective in the treatment of arterial hypotension [14]. Tamilselvan et al. [15] studied maternal cardiovascular indices and reported that the corrected ejection time (a measure of ventricular filling) did not change after the onset of spinal blockade, refuting a significant decrease in venous return as the cause of maternal hypotension. We now know that neuraxial anaesthetic techniques produce hypotension through blockade of sympathetic fibres which control vascular smooth muscle tone. Preganglionic sympathetic fibre blockade primarily causes an increase in venous capacitance, which shifts a major part of blood volume into the splanchnic bed and lower extremities reducing venous return to the heart; there is also decreased resistance in arterial pre- and postcapillary resistance vessels. The resulting decreased systemic vascular resistance contributes significantly to arterial hypotension, and Langesaeter et al. [16] showed that this was associated with an increased cardiac output [16]. Dyer et al. further showed that this increased cardiac output correlated with increased heart rate changes after vasopressor administration, emphasising the importance of heart rate as a surrogate indicator of maternal cardiac output [17,18]. Intravascular volume loading strategies Fluid administration during caesarean delivery is indicated not only to offset the dehydration of preoperative fasting but also to maintain cardiac output during the onset of spinal blockade. Most
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obstetric anaesthesiologist's fluid loading regimens centre around the timing and type of fluids. A ‘preload’ of fluid is given prior to initiating the spinal anaesthetic, and a ‘coload’ is given at the time of spinal injectate administration when cerebrospinal fluid is seen. In tandem with fluid loading, vasopressors such as phenylephrine are established as the first-line vasopressor for the treatment of maternal hypotension [12,17,19], but its discussion is beyond the scope of this article. The timing of fluid loading and the different types of available fluids (crystalloids and colloids) are discussed critically here. Timing and dosage The ideal time point for fluid administration to prevent maternal hypotension is still controversial. The primary goal of both pre- and coloading is the maintenance of maternal cardiac output and, correspondingly, maintenance of adequate placental perfusion. The physiological idea of preloading is to expand the intravascular volume of the patient before the vasodilation induces a relative hypovolaemia. Coloading with fluids is performed during or immediately after induction of spinal anaesthesia in order to replace the missing volume right ‘on time’. Interestingly, the rapid administration of 1500e2000 ml of fluid can cause release of the atrial natriuretic peptide which can cause vasodilation and initiate diuresis, thereby attenuating the effect of volume load and reducing sensitivity to vasoconstrictors during elective caesarean delivery [20]. Unwanted side effects of iatrogenic hypervolaemia have not been reported so far; however, massive bolus administration and hypervolaemia have been associated with endothelial damage in experimental settings [21]. Furthermore, Yamada et al. [22] investigated the influence of caesarean delivery on levels of the N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP) in maternal serum and described a significant increase on the third postpartum day in women undergoing caesarean compared to those that had delivered vaginally [22]. According to the authors, this rise may be caused by transient fluid overload after parturition; however, iatrogenic fluid overload caused by pre- or coloading should not be excluded as a possible reason and warrants future investigation to ascertain its true role and impact in the obstetric population. A meta-analysis by Banerjee and colleagues aimed to determine whether preload or coload influenced maternal hypotension and neonatal outcome. They included eight studies with 518 patients (preload 250 patients and coload 268 patients) undergoing spinal anaesthesia for elective caesarean delivery, and notably studies with crystalloids and colloids were both used for the analysis. Maternal hypotension occurred in 59.3% (coload) versus 62.4% (preload) (odds ratio (OR) ¼ 0.93; 95% confidence interval (CI) 0.54e1.6). No other significant differences between the groups were detected [23]. Oh et al. performed a recent prospective controlled trial with 60 women who were randomly assigned to receive either 15 ml/kg crystalloids preload or the same dose as a coload during spinal anaesthesia for caesarean. In this study, coloading turned out to reduce the incidence of maternal hypotension (53% vs. 83%, p ¼ 0.026) and nausea (27% vs. 60%, p ¼ 0.019). Vasopressor requirements were also significantly lower within the coload group as well as the drop of blood pressure after the induction of spinal anaesthesia (each p < 0.015) [24]. Commonly, the dose of fluids for pre- or coloading ranges between 10 and 20 ml/kg [25]. Though this is a widely used dosing regimen, the evidence for it remains low. As far back as 1993, Rout et al. challenged the effectiveness of this approach, showing that 20 ml/kg crystalloid prior to spinal anaesthesia did not decrease the incidence of hypotension [26]. Muzlifah et al. investigated the effects of a 10 ml/kg versus 20 ml/kg crystalloid preload and found very similar incidence of hypotension and nauseaevomiting [27]. Similarly, Ouerghi et al. also found no difference in hypotension and ephedrine requirements in women receiving 20 ml/kg crystalloid for preloading or no fluids after spinal anaesthesia for caesarean delivery [28]. It appears that the optimal dose of fluid to administer still remains elusive. However, current available data suggest that with regard to the optimal time point for fluid administration, a crystalloid preload can no longer be recommended [29]. Coloading (with both colloids and crystalloids) has proven beneficial in reducing maternal hypotension and the need for vasopressors in parturients undergoing spinal anaesthesia for caesarean delivery [30].
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Types of fluids Crystalloids and colloids are both common solutions for preloading as well as for coloading [23]. The advantages of crystalloid solutions are the almost complete absence of substance-specific side effects as well as cost effectiveness. On the other hand, the volume effect of crystalloid solutions remains low with approximately 20% remaining within the circulation [31]. Based on their physicochemical properties, the intravascular volume effect of colloid solutions is more pronounced compared to crystalloids. However, colloids also bear the risk of side effects such as anaphylaxis (especially dextrans and gelatin), and renal impairment or their usage is limited due to high costs (especially albumin). Hydroxyethyl starch (HES) is one of the most commonly used colloids for pre- and coloading in patients undergoing spinal anaesthesia for caesarean, and the use of HES for preloading is best documented [32]. Teoh et al. [33] was the first to study the effects of a colloid preload (15 ml/kg) 6% HES 130/0.4 (Voluven, Fresenius Kabi, Bad Homburg, Germany) and identical coload on maternal cardiac output and incidence of hypotension after spinal anaesthesia, using a totally non-invasive ultrasonic cardiac output monitor in parturients that was placed in the suprasternal notch to insonate the velocity of blood flow through the aortic valve and obtain stroke volume and cardiac output measurements every minute for the first 20 min after spinal anaesthesia. The colloid preload (but not coload) was associated with significant increases in cardiac output and stroke volume, but these effects were not sustained beyond 10 min and yielded no significant differences in the incidence of hypotension and phenylephrine requirements [33]. Tamilselvan et al. compared the effects of preloading with either 1.5 l crystalloid, 0.5 l 6% HES or 1.0 l 6% HES 130/0.4 (Voluven, Fresenius Kabi, Bad Homburg, Germany) on maternal cardiac output. A suprasternal Doppler flow technique was also used to measure maternal cardiac output in 5 min intervals and they showed in this trial that preload with HES increased maternal cardiac output more effectively than crystalloids; however, the effect remained significant only in the group that received 1 l of HES [15]. McDonald and colleagues compared the effects of coloading with either 1 l of Hartmann's solution or 1 l 6% HES 130/0.4 (Voluven, Fresenius Kabi, Bad Homburg, Germany), both administered quickly 5 min after spinal anaesthesia in 60 parturients. Phenylephrine was given as an infusion at the same time and titrated to maintain maternal systolic blood pressure. The study showed no significant differences in phenylephrine requirements and cardiac output between the two study groups. Unfortunately, the study was underpowered to determine differences in the incidence of hypotension (60% vs. 40%, p ¼ 0.20) [34]. Hot off the press, the results of the CAESAR trial [35] have just been published, where the effects of 6% HES 130/0.4 (Voluven, Fresenius Kabi, Bad Homburg, Germany) versus Ringer's lactate (RL) preloading before spinal anaesthesia for caesarean delivery were compared in a randomised, double-blind, multicentre trial. A total of 167 healthy parturients received 500 ml of 6% HES 130/0.4 þ 500 ml of RL (HES group) or 1000 ml of RL (RL group) intravenously (iv) before spinal anaesthesia. After spinal, iv phenylephrine boluses were administered and titrated to maintain systolic arterial pressure 95% of baseline. The primary outcome was the incidence of maternal hypotension (<80% of baseline). The CAESAR trial found the incidence of both hypotension and symptomatic hypotension (i.e., with dizziness, nausea/vomiting or both) to be significantly lower in the HES group vs. the RL group: 36.6% vs. 55.3% (one-sided p ¼ 0.025) and 3.7% vs. 14.1%. There was no significant difference in total phenylephrine requirements (median (range): 350 (50e1800) vs. 350 (50e1250) mg). The decrease in maternal haemoglobin value the day after surgery was similar in the two groups (1.2 (1.0) vs. 1.0 (0.9) g/ dl) and there was no detectable placental transfer of HES in six umbilical cord blood samples analysed in the HES group, and neonatal outcomes were comparable between the groups. This study shows that compared with a pure crystalloid preload, a mixed HESeRL preload can significantly improve the prevention of both hypotension and symptomatic hypotension, together with early phenylephrine bolus administration. The status of albumin for pre- or coloading in spinal anaesthesia seems to be negligible; other colloids like dextran and gelatin are still used despite the known rate of severe side effects. Gunusen et al. performed a study in women undergoing spinal anaesthesia for elective caesarean where 120 patients were randomly assigned to receive either preload with RL (20 ml/kg), preload with 4%
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succinylated gelatin solution (500 ml) or coload with RL (1000 ml) in combination with ephedrine infusion (1.25 mg/min). The incidence of moderate and severe maternal hypotension was significantly lower in the coload group with ephedrine compared to the preload groups (each p < 0.05) [36]. Within this trial, the coload in combination with vasopressors turned out to be more effective in the prevention of maternal hypotension than the preload with crystalloids and colloids alone. Special situations: Post-partum haemorrhage, sepsis and pre-eclampsia One of the most dangerous complications after caesarean delivery is severe post-partum haemorrhage (PPH), which is responsible for nearly one quarter of all maternal deaths worldwide. [37] The current World Health Organization (WHO) guidelines for prevention and treatment of PPH recommend a series of measures (i.e., application of oxytocin, misoprostol, tranexamic acid and intrauterine balloon tamponade); however, no recommendations regarding intravenous fluid management are given [38]. Until blood products are available, fluid resuscitation should be performed with crystalloids or colloids. Crystalloids solutions are non-osmotic and their intravascular volume effect is low. Due to this, larger amounts of crystalloids must be administered to achieve compatible effects with colloid infusion. However, the administration of large amounts of crystalloids increases the risk of pulmonary oedema, and positive fluid balance is known to be associated with increased risk of death in critically ill patients [39]. Recent studies of crystalloids and colloids in perioperative patients with large blood losses indicate that resuscitation with colloids (albumin or HES) may induce impairment of coagulation and greater haemodilution [40,41]. On the other hand, resuscitation with crystalloids resulted in a greater positive fluid balance (up to 2.5 times more) compared to patients who received colloids [41]. In summary, the decision of whether colloids or crystalloids are administered in PPH as a temporising measure to bridge the time gap until blood products are available must be evaluated weighing the pros and cons and the decision made on a case-by-case basis. Resuscitation with colloids is more effective in stabilizing haemodynamics, but it runs the risk of impaired coagulation. On the other hand, the infusion of large amounts of crystalloids may increase the risk of fluid overload and pulmonary oedema in high-risk parturients (severe pre-eclampsia and peripartum cardiomyopathy); therefore, cautious volume loading is advised. In any case, balanced solutions should be used for resuscitation to reduce the risk of hyperchloraemic acidosis and consecutive complications (i.e., renal vascular constriction) [42,43]. Summary In summary, the current available data indicate that the usage of vasopressors in combination with fluid therapy remains the pivotal technique to minimise hypotension in women undergoing neuraxial analgesia for caesarean delivery [12,30,35,44]. Obstetric anaesthesiologists are still in search of the holy grail, looking for the ‘right’ time point of fluid administration, the ‘right’ dosage of fluids and even the choice of the ‘right’ fluid. However, current data indicate that preloading with crystalloids alone is ineffective and coloading with colloids might be superior to coloading with crystalloids in preventing maternal hypotension. Gelatin and dextran must be used with caution due to severe side effects such as anaphylaxis, and HES should be avoided when renal impairment, pathological coagulation and sepsis are present.
Practice points Preloading with crystalloids alone is ineffective in reducing maternal hypotension after spinal anaesthesia. Coloading with colloids might be superior to coloading with crystalloids. Contemporary obstetric anaesthesia practice supports the increased use of cohydration, judicious use of colloids, smaller spinal doses and early phenylephrine administration.
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Research agenda Further research is warranted to investigate these combined RLeHES preload or colloid coload fluid techniques in high-risk severe pre-eclamptic patients. The use of novel automated closed-loop feedback dual drug delivery systems for vasopressor administration has shown reductions in maternal hypotension. [44] Completely non-invasive haemodynamic monitoring techniques like the USCOM [33] and NEXFIN [44] are ideal for the obstetric population.
Conflicts of interest statement Martin Westphal is the Chief Medical Officer of Fresenius Kabi. References [1] Bucklin BA, Hawkins JL, Anderson JR, et al. Obstetric anesthesia workforce survey: twenty-year update. Anesthesiology 2005;103:645e53. [2] Shibli KU, Russell IF. A survey of anaesthetic techniques used for caesarean section in the UK in 1997. Int J Obstet Anesth 2000;9:160e7. [3] Kwok SC, Teoh WH, Ithnin F. Effect of sitting position on equal-dose spinal anaesthetic for caesarean section and postpartum tubal ligation. Acta Anaesthesiol Scand 2014;58:743e50. [4] Vercauteren MP, Coppejans HC, Hoffmann VL, et al. Small-dose hyperbaric versus plain bupivacaine during spinal anesthesia for cesarean section. Anesth Analg 1998;86:989e93. [5] Ben-David B, Miller G, Gavriel R, et al. Low-dose bupivacaine-fentanyl spinal anesthesia for cesarean delivery. Reg Anesth Pain Med 2000;25:235e9. [6] Bryson GL, Macneil R, Jeyaraj LM, et al. Small dose spinal bupivacaine for Cesarean delivery does not reduce hypotension but accelerates motor recovery. Can J Anaesth 2007;54:531e7. *[7] Teoh WH, Thomas E, Tan HM. Ultra-low dose combined spinal-epidural anesthesia with intrathecal bupivacaine 3.75 mg for cesarean delivery: a randomized controlled trial. Int J Obstet Anesth 2006;15:273e8. [8] Teoh WH, Sia AT. Ultra-low dose combined spinal-epidural anaesthesia for Caesarean section in severe pre-eclampsia. Anaesthesia 2006;61:511e2. [9] Klohr S, Roth R, Hofmann T, et al. Definitions of hypotension after spinal anaesthesia for caesarean section: literature search and application to parturients. Acta Anaesthesiol Scand 2010;54:909e21. [10] Mercier FJ, Bonnet MP, De la Dorie A, et al. [Spinal anaesthesia for caesarean section: fluid loading, vasopressors and hypotension]. Ann Fr Anesth Reanim 2007;26:688e93. [11] Maayan-Metzger A, Schushan-Eisen I, Todris L, et al. Maternal hypotension during elective cesarean section and shortterm neonatal outcome. Am J Obstet Gynecol 2010;202:28. *[12] Kee WD Ngan. Prevention of maternal hypotension after regional anaesthesia for caesarean section. Curr Opin Anaesthesiol 2010;23:304e9. [13] Corke BC, Datta S, Ostheimer GW, et al. Spinal anaesthesia for Caesarean section. The influence of hypotension on neonatal outcome. Anaesthesia 1982;37:658e62. [14] Morgan PJ, Halpern SH, Tarshis J. The effects of an increase of central blood volume before spinal anesthesia for cesarean delivery: a qualitative systematic review. Anesth Analg 2001;92:997e1005. [15] Tamilselvan P, Fernando R, Bray J, et al. The effects of crystalloid and colloid preload on cardiac output in the parturient undergoing planned cesarean delivery under spinal anesthesia: a randomized trial. Anesth Analg 2009;109:1916e21. [16] Langesaeter E, Rosseland LA, Stubhaug A. Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology 2008;109:856e63. *[17] Langesaeter E, Dyer RA. Maternal haemodynamic changes during spinal anaesthesia for caesarean section. Curr Opin Anaesthesiol 2011;24:242e8. [18] Dyer RA, Reed AR, van Dyk D, et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology 2009;111:753e65. [19] Allen TK, Muir HA, George RB, et al. A survey of the management of spinal-induced hypotension for scheduled cesarean delivery. Int J Obstet Anesth 2009;18:356e61. [20] Pouta AM, Karinen J, Vuolteenaho OJ, et al. Effect of intravenous fluid preload on vasoactive peptide secretion during Caesarean section under spinal anaesthesia. Anaesthesia 1996;51:128e32. [21] Silva PL, Cruz FF, Fujisaki LC, et al. Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury. Crit Care 2010;14:R114. [22] Yamada T, Koyama T, Furuta I, et al. Effects of caesarean section on serum levels of NT-proBNP. Clin Endocrinol 2013;78: 460e5. *[23] Banerjee A, Stocche RM, Angle P, et al. Preload or coload for spinal anesthesia for elective Cesarean delivery: a metaanalysis. Can J Anaesth 2010;57:24e31.
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*[24] Oh AY, Hwang JW, Song IA, et al. Influence of the timing of administration of crystalloid on maternal hypotension during spinal anesthesia for cesarean delivery: preload versus coload. BMC Anesthesiol 2014;14:1471e2253. [25] Cyna AM, Andrew M, Emmett RS, et al. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev 2006:CD002251. [26] Rout CC, Rocke DA, 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;79:262e9. [27] Muzlifah KB, Choy YC. Comparison between preloading with 10 ml/kg and 20 ml/kg of Ringer's lactate in preventing hypotension during spinal anaesthesia for caesarean section. Med J Malaysia 2009;64:114e7. [28] Ouerghi S, Bougacha MA, Frikha N, et al. Combined use of crystalloid preload and low dose spinal anesthesia for preventing hypotension in spinal anesthesia for cesarean delivery: a randomized controlled trial. Middle East J Anesthesiol 2010;20:667e72. [29] Mercier FJ. Fluid loading for cesarean delivery under spinal anesthesia: have we studied all the options? Anesth Analg 2011;113:677e80. *[30] Loubert C. Fluid and vasopressor management for Cesarean delivery under spinal anesthesia: continuing professional development. Can J Anaesth 2012;59:604e19. [31] Ertmer C, Rehberg S, Van Aken H, et al. Physiologische Grundlagen der perioperativen Flüssigkeitstherapie. Intensivmed Up2date 2009;5:9e18. [32] Mercier FJ. Cesarean delivery fluid management. Curr Opin Anaesthesiol 2012;25:286e91. *[33] Teoh WH, Sia AT. Colloid preload versus coload for spinal anesthesia for cesarean delivery: the effects on maternal cardiac output. Anesth Analg 2009;108:1592e8. [34] McDonald S, Fernando R, Ashpole K, et al. Maternal cardiac output changes after crystalloid or colloid coload following spinal anesthesia for elective cesarean delivery: a randomized controlled trial. Anesth Analg 2011;113:803e10. *[35] Mercier FJ, Diemunsch P, Ducloy-Bouthors AS, et al. 6% Hydroxyethyl starch (130/0.4) vs Ringer's lactate preloading before spinal anaesthesia for Caesarean delivery: the randomized, double-blind, multicentre CAESAR trial. Br J Anaesth 2014 Jun 26. pii: aeu103. [Epub ahead of print]. [36] Gunusen I, Karaman S, Ertugrul V, et al. Effects of fluid preload (crystalloid or colloid) compared with crystalloid co-load plus ephedrine infusion on hypotension and neonatal outcome during spinal anaesthesia for caesarean delivery. Anaesth Intensive Care 2010;38:647e53. [37] Khan KS, Wojdyla D, Say L, et al. WHO analysis of causes of maternal death: a systematic review. Lancet 2006;367: 1066e74. *[38] Tuncalp O, Souza JP, Gulmezoglu M. New WHO recommendations on prevention and treatment of postpartum hemorrhage. Int J Gynaecol Obstet 2013;123:254e6. [39] Lee J, de Louw E, Niemi M, et al. Association between fluid balance and survival in critically ill patients. J Intern Med 2014; 14:12274. [40] Skhirtladze K, Base EM, Lassnigg A, et al. Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and Ringer's lactate on blood loss and coagulation after cardiac surgery. Br J Anaesth 2014;112:255e64. *[41] Rasmussen KC, Johansson PI, Hojskov M, et al. Hydroxyethyl starch reduces coagulation competence and increases blood loss during major surgery: results from a randomized controlled trial. Ann Surg 2014;259:249e54. [42] Rehm M, Conzen PF, Peter K, et al. [The Stewart model. “Modern” approach to the interpretation of the acid-base metabolism]. Anaesthesist 2004;53:347e57. [43] Yunos NM, Bellomo R, Hegarty C, et al. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 2012;308:1566e72. [44] Sng BL, Tan HS, Sia AT. Closed-loop double-vasopressor automated system vs manual bolus vasopressor to treat hypotension during spinal anaesthesia for caesarean section: a randomised controlled trial. Anaesthesia 2014;69:37e45.
Contents lists available at ScienceDirect
Best Practice & Research Clinical Anaesthesiology journal homepage: www.elsevier.com/locate/bean
9
Update on volume therapy in obstetrics Wendy H.L. Teoh, MBBS, FANZCA, FAMS, Senior Consultant, Adj. Assistant Professor a, b, *, Martin Westphal, MD, PhD, Professor, Chief Medical Officer c, d, Tim G. Kampmeier, MD, Research Fellow c a
Department of Women's Anaesthesia, KK Women's and Children's Hospital, Singapore Duke University e NUS Graduate Medical School, Singapore c Department of Anaesthesiology, Pain Medicine and Intensive Care, University Hospital of Muenster, Muenster, Germany d Fresenius Kabi AG, Bad Homburg, Germany b
Keywords: hypotension spinal anaesthesia caesarean delivery preload coload crystalloids colloids HES volume obstetrics
Symptomatic hypotension (maternal nausea, vomiting, dizziness and dyspnoea) during spinal anaesthesia for caesarean delivery remains a prevalent clinical problem. Severe and sustained hypotension can lead to impairment of uteroplacental perfusion, foetal hypoxia, acidosis, neonatal depression and further adverse maternal outcomes of unconsciousness, pulmonary aspiration, apnoea and cardiac arrest. Mechanical methods aimed at countering the effects of aortocaval compression do not reliably prevent maternal hypotension. Intravenous crystalloid preloading (given prior to administration of spinal anaesthesia) has poor efficacy, and focus has changed towards decreased use of crystalloid preload and ephedrine, to increased use of coload (given at the time of spinal administration) with colloids or crystalloids, and early use of phenylephrine. The recent multicentre, randomised, doubleblinded CAESAR trial demonstrated the efficacy of a mixed 500 ml 6% hydroxyethyl starch (HES) 130/0.4 þ 500 ml Ringer's lactate (RL) preload in significantly reducing hypotension, compared to a 1-l RL preload, without adverse effects on coagulation and neonatal outcomes in healthy parturients undergoing caesarean delivery under spinal anaesthesia. © 2014 Elsevier Ltd. All rights reserved.
* Corresponding author. Department of Women's Anaesthesia, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore. Tel.: þ65 81217986; Fax: þ65 62912661. E-mail addresses: [email protected] (W.H.L. Teoh), [email protected] (M. Westphal), tim.kampmeier@ gmail.com (T.G. Kampmeier).
http://dx.doi.org/10.1016/j.bpa.2014.07.004 1521-6896/© 2014 Elsevier Ltd. All rights reserved.
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Introduction In contemporary obstetric anaesthesia practice, neuraxial techniques are the preferred method for providing anaesthesia for caesarean delivery over a general anaesthetic. Compared to an epidural or combined spinaleepidural (CSE), single-shot spinal anaesthesia is most commonly employed as it is easy to perform and provides rapid-onset dense neuroblockade [1,2]. The goal for adequate surgical anaesthesia is a sensory blockade to the T5 dermatome. This is typically achieved by administration of intrathecal hyperbaric bupivacaine ranging from 10 to 12 mg with an opioid adjuvant [3]. All neuraxial techniques are associated with hypotension from the resulting sympathetic blockade. In an effort to alleviate this, the administration of fluids and vasopressors remains the cornerstone of treatment of spinal-induced hypotension, in tandem with avoidance of aortocaval compression by effecting left lateral uterine displacement and use of calf compressors to aid venous return. As the mass of local anaesthetic influences the spread of the block and causes hypotension, lower doses of 4.5e6.6 mg bupivacaine [4e6] as part of a single-shot spinal technique have previously been used for caesarean delivery, but this has raised safety concerns of whether lower doses should be used just because they can be used, due to the potential for unnecessary conversion to general anaesthesia. Lower spinal doses of local anaesthetics, however, can safely be utilised as part of a CSE technique especially if it is imperative to maintain stable intraoperative haemodynamics (e.g., severe preeclamptics and high-risk parturients with cardiac problems) as the epidural catheter allows analgesia supplementation in the event of prolonged surgical duration and breakthrough pain [7,8]. Incidence and physiology of maternal hypotension revisited Hypotension is arbitrarily defined in the literature as a systolic blood pressure <100 mmHg or <80% of the baseline value [9], and is a common sequela after spinal anaesthesia in 55e90% of parturients [10]. Reductions in blood pressure of >30% baseline have also been described in nearly 50% of women undergoing spinal anaesthesia [11]. The risk factors for hypotension include increased sympathetic tone, increasing age, obesity, higher blocks and higher birth weight, but not multiple gestation [12]. The clinical signs of spinal hypotension are usually limited to nausea/vomiting and/or dyspnoea. However, hypotension when severe and sustained can lead to impairment of uteroplacental perfusion (as the vessels are maximally dilated, of low resistance and exhibit no autoregulation), resulting in foetal hypoxia, acidosis, neonatal depression or injury [13] and adverse maternal outcomes of unconsciousness, pulmonary aspiration, apnoea and cardiac arrest. It was traditionally taught that hypotension occurred as a result of decrease in venous return and cardiac output after a spinal anaesthetic. Strategies to increase venous return (leg lifting and mechanical compression of the lower extremities) and aggressive intravascular volume loading have proven largely ineffective in the treatment of arterial hypotension [14]. Tamilselvan et al. [15] studied maternal cardiovascular indices and reported that the corrected ejection time (a measure of ventricular filling) did not change after the onset of spinal blockade, refuting a significant decrease in venous return as the cause of maternal hypotension. We now know that neuraxial anaesthetic techniques produce hypotension through blockade of sympathetic fibres which control vascular smooth muscle tone. Preganglionic sympathetic fibre blockade primarily causes an increase in venous capacitance, which shifts a major part of blood volume into the splanchnic bed and lower extremities reducing venous return to the heart; there is also decreased resistance in arterial pre- and postcapillary resistance vessels. The resulting decreased systemic vascular resistance contributes significantly to arterial hypotension, and Langesaeter et al. [16] showed that this was associated with an increased cardiac output [16]. Dyer et al. further showed that this increased cardiac output correlated with increased heart rate changes after vasopressor administration, emphasising the importance of heart rate as a surrogate indicator of maternal cardiac output [17,18]. Intravascular volume loading strategies Fluid administration during caesarean delivery is indicated not only to offset the dehydration of preoperative fasting but also to maintain cardiac output during the onset of spinal blockade. Most
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obstetric anaesthesiologist's fluid loading regimens centre around the timing and type of fluids. A ‘preload’ of fluid is given prior to initiating the spinal anaesthetic, and a ‘coload’ is given at the time of spinal injectate administration when cerebrospinal fluid is seen. In tandem with fluid loading, vasopressors such as phenylephrine are established as the first-line vasopressor for the treatment of maternal hypotension [12,17,19], but its discussion is beyond the scope of this article. The timing of fluid loading and the different types of available fluids (crystalloids and colloids) are discussed critically here. Timing and dosage The ideal time point for fluid administration to prevent maternal hypotension is still controversial. The primary goal of both pre- and coloading is the maintenance of maternal cardiac output and, correspondingly, maintenance of adequate placental perfusion. The physiological idea of preloading is to expand the intravascular volume of the patient before the vasodilation induces a relative hypovolaemia. Coloading with fluids is performed during or immediately after induction of spinal anaesthesia in order to replace the missing volume right ‘on time’. Interestingly, the rapid administration of 1500e2000 ml of fluid can cause release of the atrial natriuretic peptide which can cause vasodilation and initiate diuresis, thereby attenuating the effect of volume load and reducing sensitivity to vasoconstrictors during elective caesarean delivery [20]. Unwanted side effects of iatrogenic hypervolaemia have not been reported so far; however, massive bolus administration and hypervolaemia have been associated with endothelial damage in experimental settings [21]. Furthermore, Yamada et al. [22] investigated the influence of caesarean delivery on levels of the N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP) in maternal serum and described a significant increase on the third postpartum day in women undergoing caesarean compared to those that had delivered vaginally [22]. According to the authors, this rise may be caused by transient fluid overload after parturition; however, iatrogenic fluid overload caused by pre- or coloading should not be excluded as a possible reason and warrants future investigation to ascertain its true role and impact in the obstetric population. A meta-analysis by Banerjee and colleagues aimed to determine whether preload or coload influenced maternal hypotension and neonatal outcome. They included eight studies with 518 patients (preload 250 patients and coload 268 patients) undergoing spinal anaesthesia for elective caesarean delivery, and notably studies with crystalloids and colloids were both used for the analysis. Maternal hypotension occurred in 59.3% (coload) versus 62.4% (preload) (odds ratio (OR) ¼ 0.93; 95% confidence interval (CI) 0.54e1.6). No other significant differences between the groups were detected [23]. Oh et al. performed a recent prospective controlled trial with 60 women who were randomly assigned to receive either 15 ml/kg crystalloids preload or the same dose as a coload during spinal anaesthesia for caesarean. In this study, coloading turned out to reduce the incidence of maternal hypotension (53% vs. 83%, p ¼ 0.026) and nausea (27% vs. 60%, p ¼ 0.019). Vasopressor requirements were also significantly lower within the coload group as well as the drop of blood pressure after the induction of spinal anaesthesia (each p < 0.015) [24]. Commonly, the dose of fluids for pre- or coloading ranges between 10 and 20 ml/kg [25]. Though this is a widely used dosing regimen, the evidence for it remains low. As far back as 1993, Rout et al. challenged the effectiveness of this approach, showing that 20 ml/kg crystalloid prior to spinal anaesthesia did not decrease the incidence of hypotension [26]. Muzlifah et al. investigated the effects of a 10 ml/kg versus 20 ml/kg crystalloid preload and found very similar incidence of hypotension and nauseaevomiting [27]. Similarly, Ouerghi et al. also found no difference in hypotension and ephedrine requirements in women receiving 20 ml/kg crystalloid for preloading or no fluids after spinal anaesthesia for caesarean delivery [28]. It appears that the optimal dose of fluid to administer still remains elusive. However, current available data suggest that with regard to the optimal time point for fluid administration, a crystalloid preload can no longer be recommended [29]. Coloading (with both colloids and crystalloids) has proven beneficial in reducing maternal hypotension and the need for vasopressors in parturients undergoing spinal anaesthesia for caesarean delivery [30].
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Types of fluids Crystalloids and colloids are both common solutions for preloading as well as for coloading [23]. The advantages of crystalloid solutions are the almost complete absence of substance-specific side effects as well as cost effectiveness. On the other hand, the volume effect of crystalloid solutions remains low with approximately 20% remaining within the circulation [31]. Based on their physicochemical properties, the intravascular volume effect of colloid solutions is more pronounced compared to crystalloids. However, colloids also bear the risk of side effects such as anaphylaxis (especially dextrans and gelatin), and renal impairment or their usage is limited due to high costs (especially albumin). Hydroxyethyl starch (HES) is one of the most commonly used colloids for pre- and coloading in patients undergoing spinal anaesthesia for caesarean, and the use of HES for preloading is best documented [32]. Teoh et al. [33] was the first to study the effects of a colloid preload (15 ml/kg) 6% HES 130/0.4 (Voluven, Fresenius Kabi, Bad Homburg, Germany) and identical coload on maternal cardiac output and incidence of hypotension after spinal anaesthesia, using a totally non-invasive ultrasonic cardiac output monitor in parturients that was placed in the suprasternal notch to insonate the velocity of blood flow through the aortic valve and obtain stroke volume and cardiac output measurements every minute for the first 20 min after spinal anaesthesia. The colloid preload (but not coload) was associated with significant increases in cardiac output and stroke volume, but these effects were not sustained beyond 10 min and yielded no significant differences in the incidence of hypotension and phenylephrine requirements [33]. Tamilselvan et al. compared the effects of preloading with either 1.5 l crystalloid, 0.5 l 6% HES or 1.0 l 6% HES 130/0.4 (Voluven, Fresenius Kabi, Bad Homburg, Germany) on maternal cardiac output. A suprasternal Doppler flow technique was also used to measure maternal cardiac output in 5 min intervals and they showed in this trial that preload with HES increased maternal cardiac output more effectively than crystalloids; however, the effect remained significant only in the group that received 1 l of HES [15]. McDonald and colleagues compared the effects of coloading with either 1 l of Hartmann's solution or 1 l 6% HES 130/0.4 (Voluven, Fresenius Kabi, Bad Homburg, Germany), both administered quickly 5 min after spinal anaesthesia in 60 parturients. Phenylephrine was given as an infusion at the same time and titrated to maintain maternal systolic blood pressure. The study showed no significant differences in phenylephrine requirements and cardiac output between the two study groups. Unfortunately, the study was underpowered to determine differences in the incidence of hypotension (60% vs. 40%, p ¼ 0.20) [34]. Hot off the press, the results of the CAESAR trial [35] have just been published, where the effects of 6% HES 130/0.4 (Voluven, Fresenius Kabi, Bad Homburg, Germany) versus Ringer's lactate (RL) preloading before spinal anaesthesia for caesarean delivery were compared in a randomised, double-blind, multicentre trial. A total of 167 healthy parturients received 500 ml of 6% HES 130/0.4 þ 500 ml of RL (HES group) or 1000 ml of RL (RL group) intravenously (iv) before spinal anaesthesia. After spinal, iv phenylephrine boluses were administered and titrated to maintain systolic arterial pressure 95% of baseline. The primary outcome was the incidence of maternal hypotension (<80% of baseline). The CAESAR trial found the incidence of both hypotension and symptomatic hypotension (i.e., with dizziness, nausea/vomiting or both) to be significantly lower in the HES group vs. the RL group: 36.6% vs. 55.3% (one-sided p ¼ 0.025) and 3.7% vs. 14.1%. There was no significant difference in total phenylephrine requirements (median (range): 350 (50e1800) vs. 350 (50e1250) mg). The decrease in maternal haemoglobin value the day after surgery was similar in the two groups (1.2 (1.0) vs. 1.0 (0.9) g/ dl) and there was no detectable placental transfer of HES in six umbilical cord blood samples analysed in the HES group, and neonatal outcomes were comparable between the groups. This study shows that compared with a pure crystalloid preload, a mixed HESeRL preload can significantly improve the prevention of both hypotension and symptomatic hypotension, together with early phenylephrine bolus administration. The status of albumin for pre- or coloading in spinal anaesthesia seems to be negligible; other colloids like dextran and gelatin are still used despite the known rate of severe side effects. Gunusen et al. performed a study in women undergoing spinal anaesthesia for elective caesarean where 120 patients were randomly assigned to receive either preload with RL (20 ml/kg), preload with 4%
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succinylated gelatin solution (500 ml) or coload with RL (1000 ml) in combination with ephedrine infusion (1.25 mg/min). The incidence of moderate and severe maternal hypotension was significantly lower in the coload group with ephedrine compared to the preload groups (each p < 0.05) [36]. Within this trial, the coload in combination with vasopressors turned out to be more effective in the prevention of maternal hypotension than the preload with crystalloids and colloids alone. Special situations: Post-partum haemorrhage, sepsis and pre-eclampsia One of the most dangerous complications after caesarean delivery is severe post-partum haemorrhage (PPH), which is responsible for nearly one quarter of all maternal deaths worldwide. [37] The current World Health Organization (WHO) guidelines for prevention and treatment of PPH recommend a series of measures (i.e., application of oxytocin, misoprostol, tranexamic acid and intrauterine balloon tamponade); however, no recommendations regarding intravenous fluid management are given [38]. Until blood products are available, fluid resuscitation should be performed with crystalloids or colloids. Crystalloids solutions are non-osmotic and their intravascular volume effect is low. Due to this, larger amounts of crystalloids must be administered to achieve compatible effects with colloid infusion. However, the administration of large amounts of crystalloids increases the risk of pulmonary oedema, and positive fluid balance is known to be associated with increased risk of death in critically ill patients [39]. Recent studies of crystalloids and colloids in perioperative patients with large blood losses indicate that resuscitation with colloids (albumin or HES) may induce impairment of coagulation and greater haemodilution [40,41]. On the other hand, resuscitation with crystalloids resulted in a greater positive fluid balance (up to 2.5 times more) compared to patients who received colloids [41]. In summary, the decision of whether colloids or crystalloids are administered in PPH as a temporising measure to bridge the time gap until blood products are available must be evaluated weighing the pros and cons and the decision made on a case-by-case basis. Resuscitation with colloids is more effective in stabilizing haemodynamics, but it runs the risk of impaired coagulation. On the other hand, the infusion of large amounts of crystalloids may increase the risk of fluid overload and pulmonary oedema in high-risk parturients (severe pre-eclampsia and peripartum cardiomyopathy); therefore, cautious volume loading is advised. In any case, balanced solutions should be used for resuscitation to reduce the risk of hyperchloraemic acidosis and consecutive complications (i.e., renal vascular constriction) [42,43]. Summary In summary, the current available data indicate that the usage of vasopressors in combination with fluid therapy remains the pivotal technique to minimise hypotension in women undergoing neuraxial analgesia for caesarean delivery [12,30,35,44]. Obstetric anaesthesiologists are still in search of the holy grail, looking for the ‘right’ time point of fluid administration, the ‘right’ dosage of fluids and even the choice of the ‘right’ fluid. However, current data indicate that preloading with crystalloids alone is ineffective and coloading with colloids might be superior to coloading with crystalloids in preventing maternal hypotension. Gelatin and dextran must be used with caution due to severe side effects such as anaphylaxis, and HES should be avoided when renal impairment, pathological coagulation and sepsis are present.
Practice points Preloading with crystalloids alone is ineffective in reducing maternal hypotension after spinal anaesthesia. Coloading with colloids might be superior to coloading with crystalloids. Contemporary obstetric anaesthesia practice supports the increased use of cohydration, judicious use of colloids, smaller spinal doses and early phenylephrine administration.
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Research agenda Further research is warranted to investigate these combined RLeHES preload or colloid coload fluid techniques in high-risk severe pre-eclamptic patients. The use of novel automated closed-loop feedback dual drug delivery systems for vasopressor administration has shown reductions in maternal hypotension. [44] Completely non-invasive haemodynamic monitoring techniques like the USCOM [33] and NEXFIN [44] are ideal for the obstetric population.
Conflicts of interest statement Martin Westphal is the Chief Medical Officer of Fresenius Kabi. References [1] Bucklin BA, Hawkins JL, Anderson JR, et al. Obstetric anesthesia workforce survey: twenty-year update. Anesthesiology 2005;103:645e53. [2] Shibli KU, Russell IF. A survey of anaesthetic techniques used for caesarean section in the UK in 1997. Int J Obstet Anesth 2000;9:160e7. [3] Kwok SC, Teoh WH, Ithnin F. Effect of sitting position on equal-dose spinal anaesthetic for caesarean section and postpartum tubal ligation. Acta Anaesthesiol Scand 2014;58:743e50. [4] Vercauteren MP, Coppejans HC, Hoffmann VL, et al. Small-dose hyperbaric versus plain bupivacaine during spinal anesthesia for cesarean section. Anesth Analg 1998;86:989e93. [5] Ben-David B, Miller G, Gavriel R, et al. Low-dose bupivacaine-fentanyl spinal anesthesia for cesarean delivery. Reg Anesth Pain Med 2000;25:235e9. [6] Bryson GL, Macneil R, Jeyaraj LM, et al. Small dose spinal bupivacaine for Cesarean delivery does not reduce hypotension but accelerates motor recovery. Can J Anaesth 2007;54:531e7. *[7] Teoh WH, Thomas E, Tan HM. Ultra-low dose combined spinal-epidural anesthesia with intrathecal bupivacaine 3.75 mg for cesarean delivery: a randomized controlled trial. Int J Obstet Anesth 2006;15:273e8. [8] Teoh WH, Sia AT. Ultra-low dose combined spinal-epidural anaesthesia for Caesarean section in severe pre-eclampsia. Anaesthesia 2006;61:511e2. [9] Klohr S, Roth R, Hofmann T, et al. Definitions of hypotension after spinal anaesthesia for caesarean section: literature search and application to parturients. Acta Anaesthesiol Scand 2010;54:909e21. [10] Mercier FJ, Bonnet MP, De la Dorie A, et al. [Spinal anaesthesia for caesarean section: fluid loading, vasopressors and hypotension]. Ann Fr Anesth Reanim 2007;26:688e93. [11] Maayan-Metzger A, Schushan-Eisen I, Todris L, et al. Maternal hypotension during elective cesarean section and shortterm neonatal outcome. Am J Obstet Gynecol 2010;202:28. *[12] Kee WD Ngan. Prevention of maternal hypotension after regional anaesthesia for caesarean section. Curr Opin Anaesthesiol 2010;23:304e9. [13] Corke BC, Datta S, Ostheimer GW, et al. Spinal anaesthesia for Caesarean section. The influence of hypotension on neonatal outcome. Anaesthesia 1982;37:658e62. [14] Morgan PJ, Halpern SH, Tarshis J. The effects of an increase of central blood volume before spinal anesthesia for cesarean delivery: a qualitative systematic review. Anesth Analg 2001;92:997e1005. [15] Tamilselvan P, Fernando R, Bray J, et al. The effects of crystalloid and colloid preload on cardiac output in the parturient undergoing planned cesarean delivery under spinal anesthesia: a randomized trial. Anesth Analg 2009;109:1916e21. [16] Langesaeter E, Rosseland LA, Stubhaug A. Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology 2008;109:856e63. *[17] Langesaeter E, Dyer RA. Maternal haemodynamic changes during spinal anaesthesia for caesarean section. Curr Opin Anaesthesiol 2011;24:242e8. [18] Dyer RA, Reed AR, van Dyk D, et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology 2009;111:753e65. [19] Allen TK, Muir HA, George RB, et al. A survey of the management of spinal-induced hypotension for scheduled cesarean delivery. Int J Obstet Anesth 2009;18:356e61. [20] Pouta AM, Karinen J, Vuolteenaho OJ, et al. Effect of intravenous fluid preload on vasoactive peptide secretion during Caesarean section under spinal anaesthesia. Anaesthesia 1996;51:128e32. [21] Silva PL, Cruz FF, Fujisaki LC, et al. Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury. Crit Care 2010;14:R114. [22] Yamada T, Koyama T, Furuta I, et al. Effects of caesarean section on serum levels of NT-proBNP. Clin Endocrinol 2013;78: 460e5. *[23] Banerjee A, Stocche RM, Angle P, et al. Preload or coload for spinal anesthesia for elective Cesarean delivery: a metaanalysis. Can J Anaesth 2010;57:24e31.
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