Scholarly article on topic 'Effects of Prophylactic Continuous Infusion of Phenylephrine on Reducing the Mass of Local Anesthetic in Patients Undergoing Spinal Anesthesia for Cesarean Section'

Effects of Prophylactic Continuous Infusion of Phenylephrine on Reducing the Mass of Local Anesthetic in Patients Undergoing Spinal Anesthesia for Cesarean Section Academic research paper on "Health sciences"

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Brazilian Journal of Anesthesiology
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{Phenylephrine / "Anesthesia / Obstetrical" / "Cesarean Section" / Hypotension / Bupivacaine / "ANESTESIA: Obstétrica" / "ANESTÉSICOS: Local / bupivacaína" / "CIRURGIA: Cesárea" / COMPLICAÇÕES / "DROGAS: Fenilefrina" / "TÉCNICAS ANESTÉSICAS: Regional / subaracnóidea" / "ANESTESIA: Obstétrica" / "ANESTÉSICOS: Local / bupivacaína" / "CIRUGÍA: Cesárea" / COMPLICACIONES / "FÁRMACOS: fenilefrina" / "TÉCNICAS ANESTÉSICAS: Regional / subaracnoidea"}

Abstract of research paper on Health sciences, author of scientific article — Vinícius Pereira de Souza, José Luiz Gomes do Amaral, Maria Ângela Tardelli, Américo Massafuni Yamashita

Summary Background and objectives Reducing the mass of local anesthetic minimizes the effects of hypotension after spinal anesthesia for cesarean section and the incidence of maternal adverse events preserving fetal well-being, but it may result in insufficient anesthesia. Hypotension associated with greater masses of subarachnoid anesthesia can be controlled by prophylactic continuous infusion of phenylephrine. The effects of prophylactic continuous infusion of phenylephrine on pressure control on maternal and fetus results in cesarean sections with different doses of hyperbaric bupivacaine in spinal anesthesia. Methods A non-randomized prospective study of 60 gravidas at term scheduled for elective cesarean sections was undertaken. Patients were allocated into two groups depending on hyperbaric bupivacaine dose administered for spinal anesthesia, 12 or 8 mg, along with 5 μg of sufentanil and 100 μg of morphine. Patients were hydrated with 10 mL.kg-1 of Ringer's lactate before the anesthesia. Shortly after, continuous infusion of 100 μg.min-1 of phenylephrine was initiated to maintain blood pressure at baseline levels. The following parameters were evaluated: level of anesthetic blockade, consumption of vasopressors, incidence of maternal events, and conditions of the newborn. Results Maternal data was similar in both groups regarding the level of anesthetic blockade, phenylephrine consumption along time, incidence of hypotension, hypertension, bradycardia, nausea, vomiting, dyspnea, pain, and tremors. Conceptual data showed similarities between both groups regarding blood gases and umbilical vein lactate levels. The pH of all newborns was > 7.2. Conclusions On maintaining the blood pressure with prophylactic continuous infusion of phenylephrine the incidence of maternal adverse events and conditions of birth do not differ whether spinal anesthesia is performed with 12 mg or 8 mg of hyperbaric bupivacaine.

Academic research paper on topic "Effects of Prophylactic Continuous Infusion of Phenylephrine on Reducing the Mass of Local Anesthetic in Patients Undergoing Spinal Anesthesia for Cesarean Section"

Rev Bras Anestesio! 2011; 61: 4: 409-424

Effects of Prophylactic Continuous Infusion of Phenylephrine on Reducing the Mass of Local Anesthetic in Patients Undergoing Spinal Anesthesia for Cesarean Section

Vinfcius Pereira de Souza, TSA 1, José Luiz Gomes do Amaral, TSA 2, Maria Ângela Tardelli, TSA 3, Américo Massafuni Yamashita, TSA 4

Summary: Souza VP, Amaral JLG, Tardelli MA, Yamashita AM - Effects of Prophylactic Continuous Infusion of Phenylephrine on Reducing the Mass of Local Anesthetic in Patients Undergoing Spinal Anesthesia for Cesarean Section.

Background and objectives: Reducing the mass of local anesthetic minimizes the effects of hypotension after spinal anesthesia for cesarean section and the incidence of maternal adverse events preserving fetal well-being, but it may result in insufficient anesthesia. Hypotension associated with greater masses of subarachnoid anesthesia can be controlled by prophylactic continuous infusion of phenylephrine. The effects of prophylactic continuous infusion of phenylephrine on pressure control on maternal and fetus results in cesarean sections with different doses of hyperbaric bupivacaine in spinal anesthesia.

Methods: A non-randomized prospective study of 60 gravidas at term scheduled for elective cesarean sections was undertaken. Patients were allocated into two groups depending on hyperbaric bupivacaine dose administered for spinal anesthesia, 12 or 8 mg, along with 5 ^g of sufentanil and 100 ^g of morphine. Patients were hydrated with 10 mL.kg-1 of Ringer's lactate before the anesthesia. Shortly after, continuous infusion of 100 ^g.min-1 of phenylephrine was initiated to maintain blood pressure at baseline levels. The following parameters were evaluated: level of anesthetic blockade, consumption of vasopressors, incidence of maternal events, and conditions of the newborn.

Results: Maternal data was similar in both groups regarding the level of anesthetic blockade, phenylephrine consumption along time, incidence of hypotension, hypertension, bradycardia, nausea, vomiting, dyspnea, pain, and tremors. Conceptual data showed similarities between both groups regarding blood gases and umbilical vein lactate levels. The pH of all newborns was > 7.2.

Conclusions: On maintaining the blood pressure with prophylactic continuous infusion of phenylephrine the incidence of maternal adverse events and conditions of birth do not differ whether spinal anesthesia is performed with 12 mg or 8 mg of hyperbaric bupivacaine.

Keywords: Phenylephrine; Anesthesia, Obstetrical; Cesarean Section; Hypotension; Bupivacaine.

[Rev Bras Anestesiol 2011;61(4): 409-424] ©Elsevier Editora Ltda.

INTRODUCTION

Spinal anesthesia is the technique of choice commonly used for cesarean section worldwide 1-4. However, hypotension remains the main complication related with this technique 5-7, associated with several maternal (nausea, vomiting, dyspnea, and discomfort) and fetal adverse events (acidosis and fetal suffering, neurologic injuries, and death) 8-9.

Received from Hospital Mater Dei, Belo Horizonte, MG, Brazil.

1. Intensive Care Specialist - AMIB; Coordinator of the Servigo de Anestesiologia do Hospital Mater Dei

2. Professor of the Disciplina de Anestesiologia, Dor e Terapia Intensiva of Escola Paulista de Medicina of Universidade Federal Estadual Paulista, EPM-UNIFESP

3. Associate Professor of the Disciplina de Anestesiologia, Dor e Terapia Intensiva of EPM-UNIFESP

4. Assistance Professor of the Disciplina de Anestesiologia, Dor e Terapia Intensiva of EPM-UNIFESP

Submitted on August 12, 2010. Approved on December 28, 2010.

Correspondence to:

Dr. Vinicius Pereira de Souza

Rua Araguari, 1331/1401

Santo Agostinho

30190111 - Belo Horizonte, MG, Brazil E-mail: vinicius.ps@terra.com.br

Several strategies have been used to prevent spinal anesthesia-related hypotension, and among them we highlight the reduction of the mass of local anesthetic and prophylactic continuous infusion of phenylephrine. Addition of liposoluble opioids to spinal anesthesia allowed the reduction of the mass of local anesthetic administered 10, incidence, severity, and duration of hypotension, consumption of vasopressors, and duration of motor blockade 11-16. Infusion of phenylephrine has proven to be safe and effective, and it does not have the risk of insufficient anesthetic blockade secondary to reduction in the mass of local anesthetic 17-19.

The objective of the present study was to comparatively evaluate the effects of prophylactic continuous infusion of phenylephrine on maternal and fetal results of different masses of local anesthetic usually administered in spinal anesthesia for elective cesarean section.

METHODS

After approval by the Ethics Councils of Hospital Mater Dei in Belo Horizonte/MG, and UNIFESP in Sao Paulo/SP, and patients signing of informed consent, a prospective non-

randomized clinical assay was performed with 60 gravidas at term (gestation with more than 37 weeks), physical status I and II according to the American Society of Anesthesiologists (ASA), scheduled for elective cesarean sections.

Exclusion criteria were as follows: obesity with body mass index greater than 30 kg.m-2; history of preeclampsia and/or prior hypertension; presence of cardiac or cerebrovascular diseases; rupture of the amniotic sac; presence of signs of labor onset; and situations involving contraindications for su-barachnoid anesthesia.

Patients were allocated into two groups, G12 and G8, depending on the dose of hyperbaric bupivacaine administered.

Monitoring consisted of cardioscopy, pulse oximetry, and non-invasive blood pressure. An 18G catheter was used for venipuncture. A vesical catheter was used according to the surgical team's criterion.

Ringer's lactate 10 mL.kg-1 10 to 15 minutes before anesthesia and a total volume of 1,000 mL until delivery was used for volemic expansion.

Patients were on the sitting position for spinal anesthesia; the space between the second and third lumbar vertebrae was punctured with a pencil tip 27G needle. After puncture, patients were placed in dorsal decubitus with the uterus deviated to the left by placing a wedge below the right hip.

In G12 group, 12 mg of hyperbaric bupivacaine were administered, while in G8 group, 8 mg were administered. In both groups, 5 ^g of sufentanil and 100 ^g of morphine were added to the anesthetic solution, which was injected at a rate of 1 mL every 10 seconds.

Blood pressure was obtained through the oscillometric method, with the cuff of the device on the left arm. The baseline blood pressure was obtained with the patient in dorsal decubitus, without the wedge under her right hip, after she was admitted to the operating room. After neuraxial block, blood pressure was automatically measured every 3 minutes until delivery.

A syringe pump was used for continuous infusion of phenylephrine immediately after spinal anesthesia. Initially, the rate of infusion of phenylephrine was adjusted to 100 ^g.min-1, and followed by adjustments to maintain blood pressure at baseline levels. The vasopressor infusion was stopped after fetal extraction, immediately after clamping the umbilical cord.

In case of an abrupt fall in systolic blood pressure by more than 10% of baseline levels, a bolus of 50 ^g phenylephrine was administered. Hypotension was defined as a fall greater than 20% in baseline levels.

On the other hand, hypertension was defined as an increase in systolic blood pressure greater than 20% in baseline levels. In the presence of hypertension, phenylephrine infusion was stopped, to be reinitiated immediately after blood pressure returned to baseline levels.

Bradycardia was defined as a reduction in heart rate below 50 bpm. Whenever bradycardia was accompanied by normal blood pressure and/or hypertension, the infusion of phenylephrine was stopped. If bradycardia was accompanied by hypotension, 1.0 mg of intravenous atropine was administered.

In case of pain and discomfort any time during the surgery an intravenous bolus of 10 ^g of sufentanil associated with 0.2 mg.kg-1 of ketamine was administered.

Immediately after delivery, double clamping of a segment of 10 to 15 cm of the umbilical cord was performed to collect blood samples from the umbilical vein and artery in a heparin-containing syringe for arterial blood gases and lactate levels. Samples were analyzed up to 60 minutes after being collected.

The anesthetic process predicted levels of sensorial blockade to pinprick in both middle axillary lines 5 to 10 minutes after subarachnoid anesthesia.

Time intervals recorded during anesthesia were as follows: time between end of subarachnoid anesthesia and delivery in minutes; time between uterotomy and delivery in seconds; and time between end of subarachnoid anesthesia and cesarean section in minutes.

The total mass of vasopressor administered, number of hypotensive, hypertensive, and bradycardia episodes; need of atropine; maternal adverse events, such as nausea, vomiting, dyspnea, pain, discomfort, and tremors; and the need of anesthetic complementation until the end of the cesarean section were recorded.

In newborns, the following parameters were analyzed: weight; Apgar index in the first and fifth minutes; and blood gases and lactate levels in umbilical artery and vein.

The Student t test was used in the statistical analysis of continuous numerical variables investigating group homogeneity regarding age, gestational age, weight, initial systolic blood pressure and heart rate, and volume and total mass of vasopressors administered, as well as arterial blood gases and lactate levels in umbilical vessels. Times between anesthesia and delivery and uterotomy and delivery were evaluated by the Mann-Whitney test. A level of 0.05% was considered significant.

The tendency Chi-square test was used to analyze the in-tergroup differences in sensorial blockade level. The incidence of maternal adverse events and the need of atropine were analyzed by the Fisher and Chi-square tests.

Excel 97-2003 and SPSS 16.0 were the statistical software used.

Considering a level of significance of 5%, power of 80%, and the primary objective of blood pressure control by the occurrence of nausea and vomiting, it was calculated a sample size of 23 patients per group. Thirty patients in each group were investigated, as data collection was made before calculating the size of the sample.

RESULTS

The main indications for cesarean sections are shown in Table I. Regarding physical status, it was observed that, in groups G12 and G8, 73.3% and 86.7% of patients were ASA I, and 22.7% and 13.3% were ASA II, respectively.

Both groups were homogeneously regarding patient characteristics (Table II).

A difference between groups regarding sensorial blockade level 5 and 10 minutes after subarachnoid administration (Figures 1 and 2) was not observed. In both groups sensorial blockade 5 and 10 minutes after the administration of local anesthetic was at T6 and T4, respectively.

Mean anesthesia-delivery times was 23.3 minutes in G12, and 18.6 minutes in G8 (Table III) with a significant difference between both groups (p = 0.0009) (Figure 3). Uterotomy-delivery time did not show a significant difference between both groups (p = 0.695), with a mean of 75.0 seconds in G12, and 73.9 seconds in G8. The mean total duration of the

Table I - Indications for Cesarean Section _Gi2 (n)

G« (n)

Prior cesarean section 13

Cephalopelvic disproportion 11

Maternal request 4

Others* 2

15 9 2 4

Results presented as number of patients.

*Others: Uterine myomatosis, oligohydramnios, fetal macrosomia.

Table II - Patient Characteristics

■s 15-

Dermatome

□ G12 □ G8

Figure 1 - Sensorial Level 5 Minutes After Subarachnoid Injection in G12 e G8.

G12: 12 mg group; G8: 8 mg group.

G12 G8 P

Age (years) 31 ± 6.2 (16-43) 31.1 ± 5.8 (23-43) 0.931

Weight (kg) 73.3 ± 10 (60-95) 74.5 ± 11.8 (54-104) 0.672

Height (cm) 161.1 ± 20 (160-176) 163 ± 5.1 (153-171) 0.628

Gestational age (weeks) 38.6 ± 0.9 38.3 ± 0.7 0.154

Baseline blood pressure (mmHg) 122.3 ± 10.3 (105-42) 121.7 ± 10.6 (100-141) 0.825

Baseline heart rate (bpm) 87.3 ± 12.3 (64-108) 87.9 ± 13.9 (60-115) 0.875

Results presented as mean ± standard deviation and (minimum - maximum).

tD 15 H

3 10 ^ m

Dermatome

□ G12

□ G8

Figure 2 - Sensorial Blockade 10 Minutes After the Subarachnoid

Injection in G12 e G8.

G12: 12 mg group; G8: 8 mg group.

Evolution of Mean Systolic Blood Pressure (mmHg) and Heart Rate (bpm) along Time (min) in G12 and G8

e r u s s e r P

S t ° ®

£ ~ « S ye

6 9 12 15 18 21 24 Time (min)

—SBP G12 —•—SBP G8 —A—HR G12 —0—HR G8

Figure 3 - Evolution of Mean Systolic Blood Pressure (mmHg) and Heart Rate (bpm) along Time (min) in G12 and G8. SBP: Systolic blood pressure; HR: heart rate.

procedure, measured by the anesthesia-end of surgery time was 72.44 and 67.33 minutes in G12 and G8, respectively, without a significant difference between groups (p = 0.171) (Table III).

The total mass of phenylephrine administered was significantly different (p = 0.0023) between G12 (mean of 1,024.3 ^g) and G8 (mean of 794.2 ^g). Comparing the relationship between the total mass of phenylephrine administered to the anesthesia-delivery time (phenylephrine infusion time), differences between groups were not observed (p = 0.9753). Differences between both groups regarding the incidence of hypotension and hypertension were not observed. The incidence of bradycardia was similar in both groups, without the need of atropine (Table IV).

The greatest and lowest level of systolic blood pressure and heart rate recorded did not differ between groups (Table V). Differences in the evolution of blood pressure and heart rate levels between both groups were not observed (Figure 3).

Differences in maternal adverse events were not observed between groups (Table VI). Only one patient in G12 (3.3%) developed nausea and one patient in G8 (3.3%) developed dyspnea. Patients did not complain of pain, discomfort, or developed vomiting until the end of the procedure. Anesthetic supplementation was not necessary.

Data on newborns were homogenous in both groups (Table VII). Only one newborn in G12 had an Apgar of three in the first minute. All other newborns had an Apgar of seven in the first minute. On the fifth minute, they all scored more than seven.

Blood gases and lactate levels in the umbilical vein and artery were measured at a mean time of 20.29 minutes and 19.71 minutes in G12 and G8, respectively, after blood collection. The greatest time interval between blood collection and exams was 42 and 43 minutes in G12 and G8, respectively.

Table III - Anesthetic-Surgical Times

G12 G8 p

Anesthesia-delivery (minutes) 23.3 ± 5.6 18.6 ± 4.7 0.0009*

Uterotomy-delivery (seconds) 75 ± 53.6 73.9 ± 60.8 0.695

Anesthesia-end of surgery (minutes) 72.44 ± 15.70 67.33 ± 12.74 0.17

Results presented as mean ± standard deviation.

"Significant statistics: p < 0.05.

Table IV - Consumption of Vasopressors and Hemodynamic Variables

G12 G8 p

Total mass of phenylephrine administered (^g) 1,024.3 ± 277.4 794.4 ± 281.1 0.0023*

Mass of phenylephrine /infusion time (^g.min-1) 44.06 ± 6.63 44.18 ± 13.97 0.957

Incidence of hypotension** 7 (23%) 2 (6.6%) 0.145

Incidence of hypertension** 11 (33.6%) 5 (16.7%) 0.144

Bradycardia** 4 (13.4%) 5 (16.7%) 0.735

Administration of atropine** 0 (0%) 0 (0%) 1

Results presented as mean ± standard deviation for phenylephrine consumption. Other data are (**) presented as n and (%). *Significant statistics: p < 0.05.

Table V - Maximum and Minimum Blood Pressure and Heart Rate in G12 e G8

G12 G8 p

Systolic blood pressure

Maximum (mmHg) 140.4 ± 10.8 (122-167) 137.2 ± 11.0 (115-155) 0.25

Mrnrnum (mmHg) 108.5 ± 12.0 (77-140) 112.7 ± 10.3 (91-134) 0.15

Heart rate

Maximum (bpm) 90.1 ± 11.8 (66-115) 89.6 ± 13.1 (66-112) 0.88

Minimum (bpm) 60.7 ± 7.9 (48-75) 60.8 ± 10.2 (46-89) 0.98

Results presented as mean ± standard deviation (maximum and minimum).

Table VI - Adverse Maternal Events

G12 G8 P

Nausea 1 (3.3%) 0 (0%) 1

Vomiting 0 (0%) 0 (0%) 1

Pain 0 (0%) 0 (0%) 1

Dyspnea 0 (0%) 1 (3.3%) 1

Tremors 4 (13.3%) 6 (20%) 0.729

Results presented as number of episodes (percentage).

412 Revista Brasileira de Anestesiologia

Vol. 61, No 4, July-August, 2011

Table VII - Newborn Characteristics

G G 8 P

Weight (g) 3,137.6 ± 352.9 3,206.1 ± 405.2 0.488

APGAR 1 min < 7 1 (3.3%)* 0 (0%)* 1

APGAR 5 min < 7 0 (0%)* 0 (0%)* 1

Umbilical artery blood gases:

pH 7.33 ± 0.04 7.33 ± 0.04 0.839

pCO2 (mmHg) 45.8 ± 8.1 45.9 ± 6.9 0.925

Bicarbonate (mmol.L-1) 24 ± 4.5 23.8 ± 2.0 0.819

BE (mmol.L-1) -1.2 ± 1.4 -1.3 ± 1.7 0.941

Arterial lactate (mmol.L-1) 1.8 ± 0.4 1.9 ± 0.5 0.781

Umbilical vein blood gases:

pH 7.35 ± 0.04 7.35 ± 0.05 0.839

pCO2 (mmHg) 42.7 ± 6.1 42.7 ± 6.9 0.955

Bicarbonate (mmol.L-1) 23.6 ± 3.4 22.8 ± 1.9 0.275

BE (mmol.L-1) -1.7 ± 1.3 -2.1 ± 1.7 0.412

Venous lactate (mmol.L-1) 1.8 ± 0.4 1.9 ± 0.6 0.361

Fetal acidosis (pH < 7.2) 0 (0%)* 0 (0%)* 1

Results presented as mean ± standard deviation. * Results are presented as number and percentage.

DISCUSSION

This study questions the benefits of reducing the mass of local anesthetic in spinal anesthesia for elective cesarean sections with prophylactic continuous infusion of phenylephrine for maternal and fetal results.

In clinical practice the choice of the mass of local anesthetic administered is made intuitively according to the agility and experience of surgical teams, considering the greater dispersion of anesthetics in gravidas. The choice of higher and lower anesthetic mass, 12 mg or 8 mg, was made for surgical teams knowingly with greater and lower surgical times, respectively. The homogeneity of sample characteristics and study groups decreased the bias due to non-randomized group selection.

The choice of 12 mg of hyperbaric bupivacaine is justified, as it is a dose traditionally used in spinal anesthesia for cesarean sections in clinical practice. On the other hand the dose of 8 mg associated with liposoluble opioids represents a 33.33% reduction in total mass of bupivacaine, and it can be safely used in spinal anesthesia for cesarean sections 1220. A recent study reported that doses from 5 mg to 7 mg of hyper-baric bupivacaine associated with opioids can only be used in combined anesthesia, and the presence of epidural catheter for analgesic supplementation is mandatory. The dose of 8 mg used in the present study is above the minimal limit recommended by the authors, and it can be safely administered in single-puncture spinal anesthesia without the need for combined anesthesia. Only one study, by Bryson et al. 22, demonstrated the safety of using 4.5 mg of isobaric bupivacaine associated with 50 ^g of fentanyl and 200 ^g of morphine in spinal anesthesia for cesarean sections. Therefore, the repetition of this data is necessary to change conducts in clinical practice.

The association of liposoluble opioids and local anesthetic in spinal anesthesia for cesarean sections promotes better quality of the anesthetic blockade with effective reduction in

the visceral component of pain during cesarean sections 23. Subarachnoid doses greater than 5 ^g of sufentanil are associated with improvement in the quality of the anesthetic blockade, but they increase significantly the incidence of side effects, such as pruritus 2324. The association of sufentanil and local anesthetic for spinal anesthesia reduces the latency of the anesthetic blockade, improves the intraoperative quality, and provides analgesia in the immediate postoperative period, lasting approximately 6 hours 25.

Morphine was associated with the anesthetic solution to provide longer lasting analgesia in the immediate postoperative period. Because morphine is a hydrosoluble opioid, its onset of action is delayed and longer lasting when compared to liposoluble opioids 10. A standardized dose of 100 ^g of morphine was used because studies have reported that higher doses do not add benefits and they are associated with greater incidence of pruritus 26-28.

One of the main changes on the concepts related to the administration of spinal anesthesia for cesarean section is related to the prevention of hypotension after spinal anesthesia by the prophylactic infusion of alpha1-adrenergic drugs to achieve minimal reductions in blood pressure. Prophylactic continuous administration of phenylephrine reduces the incidence of maternal nausea and vomiting resulting in greater umbilical artery and vein pH 17. In the present study, it was decided to use prophylactic continuous infusion of phenyle-phrine for hemodynamic control aiming at minimal reduction in blood pressure.

Several reports in the literature have shown the benefits of reducing the mass of local anesthetic in spinal anesthesia for cesarean section, with a reduction in the incidence of maternal hypotension, nausea, and vomiting, besides reduced consumption of vasopressors 12>1316>22 2s. However, in those studies vasopressors were administered whenever the blood pressure showed a reduction equal or greater than 30% in baseline systolic blood pressure or a systolic blood pressure

below 90 mmHg after spinal anesthesia. But this strategy no longer represents the gold standard in spinal anesthesia for cesarean section.

On the other hand, studies that used the strategy of prophylactic phenylephrine for pressure control are rare in this context of reducing the mass of local anesthetic as their focus was basically on different modes of administration of pheny-lephrine. Thus, a fixed dose of local anesthetic was used varying the mode of administration of this vasopressor 19.

In the present study, sensorial blockade levels were measured 5 and 10 minutes after the subarachnoid injection, suggesting similar dispersion of the anesthetic in the study groups. After 10 minutes, sensorial level reached T6 in both groups. This level of blockade is considered safe for the beginning of a surgery 30.

Sympathetic blockade levels can reach up to four derma-tomes above the sensorial blockade 31. The blockade level 10 minutes (T6 in both groups) after spinal anesthesia blocks practically all sympathetic chain. Dispersion of local anesthetics in the subarachnoid space can extend for up to 20 to 25 minutes after subarachnoid injection 31. Considering the level of blockade at 10 minutes, the additional dispersion of the local anesthetic probably did not influence the incidence of hypotension and consumption of vasopressors.

Total phenylephrine consumption was greater in G12 than in G8. This difference can be explained by the non-randomization of the study groups and greater local anesthetic mass administered by those surgical teams with longer surgical times. The group of 12 mg hyperbaric bupivacaine showed greater time interval between the subarachnoid administration and fetal extraction and, therefore, greater infusion time and greater total consumption of phenylephrine.

The difference in total phenylephrine consumption cannot be attributed to differences in sensorial blockade level due to the homogeneity of anesthetic blockade levels, which were not different between groups.

Total phenylephrine consumption was 1,024 ^g in G12, and it was demonstrated to be safe for use in spinal anesthesia for cesarean section. The administration of a total mass of phenylephrine up to 1,500 ^g has been described in literature as not causing maternal and fetal adverse events 17. Currently, phenylephrine is the first-line drug for prevention of hypotension after spinal anesthesia 32.

Variation in the mass of the local anesthetic administered did not have impact in the reduction or increase in vasopressor consumption by unit of time. Adjusting the total phenylephrine consumption to the infusion time (^g.min-1), differences were not observed between groups, confirming that the greatest total consumption in G12 was due to the longer infusion time. However, studies published have demonstrated a reduction in vasopressor consumption with the reduction in local anesthetic mass 12-16. The difference regarding the results in our study can be explained by the fact that the authors adopted a therapeutic strategy of vasopressor administration.

Several publications used a fixed dose of local anesthetic and evaluated different doses and administration routes of phenylephrine isolatedly or combined with other vasopres-

sors when analyzing its effects and adverse events 17 19 33. Recently, the effects of prophylactic phenylephrine infusion were analyzed in 80 patients who underwent spinal anesthesia for cesarean section with 10 mg or 7 mg of isobaric bupivacaine associated with 4 mcg of sufentanil 34. The rate of phenylephrine infusion was lower than the rate of infusion in the present study. The authors observed that smaller hemo-dynamic changes are associated with the administration of low doses of local anesthetic combined with continuous infusion of phenylephrine.

The incidence of hypotension observed with the protocol of prophylactic phenylephrine administration is in agreement with the study of Ngan Kee et al. 17, who observed a 16% incidence of hypotension, in which they defined hypotension as a fall greater than 20% in baseline systolic blood pressure after the subarachnoid administration of 10 mg of bupivacaine.

Although we observed low incidence of hypotension in G8, a study published by the same group of Ngan Kee et al. 19 observed a smaller incidence of hypotension, 1.2%. This difference can be explained by the infusion of a large volume of crystalloid (2,000 mL of Ringer's lactate) before the administration of spinal anesthesia, contrary to the maximum volume of 1,000 mL of Ringer's lactate administered up to fetal extraction in our study.

The main maternal adverse effects caused by the continuous infusion of phenylephrine were hypertension and bra-dycardia. The mean incidence of hypertension in both groups was lower than the results reported in literature, whose incidence can reach up to 47% without negative maternal and fetal repercussions 19.

In literature the incidence of bradycardia with phenylephrine infusion reaches up to 5% 1535, which might require the administration of atropine. Bradycardia may result from phenyle-phrine-induced increase in peripheral vascular resistance that leads to an increase in left ventricular afterload and reduction in heart rate 36. In the present study a greater incidence of bradycardia was observed in the 8 mg (16.7%) group. Ngan Kee et al. 19 reported a 24.8% incidence of bradycardia with a 100 ^g.min-1 infusion of phenylephrine.

Our results show that episodes of bradycardia were not followed by hemodynamic repercussions (hypotension), and they did not require the administration of atropine, only interruption of the infusion of vasopressor. These data are also in agreement with the literature 15 19 35. Other cardiac arrhythmias such as ventricular bigeminism were not observed 37.

The incidence of maternal adverse events was minimal; only 1/30 (3.3%) had an episode of nausea in the group of greater mass of local anesthetic. This episode of nausea was observed along with an episode of hypotension with a reduction in systolic blood pressure from 115 mmHg to 90 mmHg. The incidence of nausea recorded in both groups was smaller than that reported in literature whose incidence can reach up to 16% 17.

The low incidence of nausea and vomiting observed is secondary to the strict blood pressure control with liposoluble opioids added to the spinal anesthesia solution. Approximately 80% of episodes of nausea and vomiting are secondary

to hypotension. Other causes of intraoperative nausea and vomiting include surgical stimuli, such as peritoneal and intraabdominal organ manipulation and traction. Addition of suba-rachnoid analgesic to the local anesthetic solution improves the quality of anesthetic blockade and reduces the incidence of intraoperative nausea and vomiting 23. Non-prophylactic pressure control strategies after spinal anesthesia have higher incidence of maternal adverse events, such as nausea and vomiting, which can afflict up to 40% of patients 12,13,36,38.

In this study patients did not complain of pain and/or discomfort during surgical procedure, and they did not require anesthetic supplementation which demonstrates the safe use of 8 mg hyperbaric bupivacaine in single-puncture spinal anesthesia associated with 5 ^g sufentanil and 100 ^g morphine in cesarean sections with a mean duration of 67 minutes. Masses of hyperbaric bupivacaine of 5 mg and 7 mg can be administered in cesarean sections with 50- and 70-minute duration 21. However, for such doses combined anesthesia is recommended 21.

Fetal results did not show a significant difference when the mass was reduced from 12 mg to 8 mg. Only one newborn in the 12-mg group had an Apgar of three in the first minute, On this cesarean section, the uterotomy-delivery time was 5 minutes and 33 seconds, resulting in a greater period of ischemia, justifying the low initial score; pH of the umbilical artery and vein in this fetus was higher than 7.20, and the Apgar score on the fifth minute was 9 without evidence of fetal suffering.

Mean pH in the umbilical artery and vein were 7.33 and 7.35 in both groups. These levels are higher than those in other studies 17, and they are in disagreement with the metaanalysis of Reynolds and Seed 39, for whom spinal anesthesia for cesarean section would be associated with worsening fetal acid-base status when compared to epidural and general anesthesia. The authors evaluated 27 studies including studies from the decade of 1960, and concluded that the pH of patient undergoing spinal anesthesia was lower than that of patients undergoing general and epidural anesthesia, and this difference was 0.015. The concepts and strategies of spinal anesthesia in the decade of 1960 were different from current ones, and the administration of ephedrine could be responsible for this difference in results. After crossing the placental

barrier, ephedrine would increase fetal metabolisms and release catecholamines 9 40-42. a large placental transference of ephedrine is observed when compared to phenylephrine resulting in fetal repercussions with a significant increase in circulating catecholamines 43. The safety of using phenylephrine in spinal anesthesia for cesarean section was observed, and these results have been confirmed by several clinical and experimental studies 44 47. We demonstrated that the use of alpha1-adrenergic drugs is safe and effective, and the umbilical artery and vein pH was 7.33 and 7.35 in G12 and G8, respectively. This pH revealed good delivery conditions related with spinal anesthesia, as well as the safety of administering phenylephrine on fetal acid-base status 32.

Umbilical artery and vein blood were collected by the double-clamping technique with a heparinized syringe, and all samples were analyzed within 60 minutes after collection. The American College of Gynecology and Obstetrics recommends analysis of the samples within 60 minutes of collection in a heparinized syringe 48. Studies on the effects of time on the results of blood gases in the umbilical artery and vein observed that 60 minutes after the collection pH levels did not change 49; however, levels of pCO2 were significantly reduced, while pO2 increased. The study questions the efficacy of reducing the mass of local anesthetic on maternal and fetal results in patients undergoing spinal anesthesia for elective cesarean section with strict blood pressure control with infusion of phenylephrine. Prevention of hypotension by using a prophylactic strategy, such as infusion of vasopressors, substitutes the beneficial effects of reducing the mass of local anesthetics on maternal and fetal results.

However, this study did not assess occasional differences between the maternal results that could be observed after fetal extraction, such as the time of regression of the motor blockade, use of uterotonic drugs, and postoperative analgesia; these data would also be related to maternal satisfaction 22 50.

We conclude that, in patients undergoing spinal anesthesia for elective cesarean section with strict blood pressure control with phenylephrine, the variation in the mass of hyperbaric bupivacaine from 12 mg to 8 mg is not associated with differences in the incidence of adverse maternal events, quality of anesthetic blockade until the end of the procedure, and conditions of fetal delivery.

Rev Bras Anestesio! 2011; 61: 4: 409-424

Efeitos da Infusáo Continua Profilática de Fenilefrina sobre a Estratégia de Redugáo da Massa de Anestésico Local em Pacientes Submetidas a Raquianestesia para Cesariana

Vinícius Pereira de Souza, TSA 1, José Luiz Gomes do Amaral, TSA 2, Maria Ángela Tardelli, TSA 3, Américo Massafuni Yamashita, TSA 4

Resumo: Souza VP, Amaral JLG, Tardelli MA, Yamashita AM - Efeitos da Infusáo Continua Profilática de Fenilefrina sobre a Estratégia de Re-dugáo da Massa de Anestésico Local em Pacientes Submetidas a Raquianestesia para Cesariana.

Justificativa e objetivos: A redugáo da massa de anestésico local minimiza os efeitos da hipotensáo arterial pós-raquianestesia para cesariana e a incidencia de eventos adversos maternos preservando o bem-estar fetal, mas pode resultar em anestesia insuficiente. A hipotensáo asso-ciada as maiores massas de anestésico subaracnóideo pode ser controlada com infusáo continua profilática de fenilefrina. Foram avaliados os efeitos da infusáo continua profilática de fenilefrina para controle pressórico sobre os resultados maternos e conceptuais em cesarianas com diferentes doses de bupivacaina hiperbárica na raquianestesia.

Método: Realizou-se ensaio clínico prospectivo, náo aleatório, com 60 gestantes a termo admitidas para cesariana eletiva. Alocaram-se as pacientes em dois grupos, na dependencia da dose de bupivacaina hiperbárica administrada na raquianestesia, 12 ou 8 mg, acrescida de 5 ^g de sufentanil e 100 ^g de morfina. Realizou-se hidratagáo com 10 mL.kg-1 de solugáo lactato de Ringer antes do bloqueio. Logo após, iniciou-se infusáo continua de 100 ^g.min-1 de fenilefrina, mantendo a pressáo arterial nos valores basais. Avaliaram-se: nivel de bloqueio anestésico, o consumo de vasopressores, incidencia de eventos adversos maternos e condigoes do recém-nascido.

Resultados: Os dados maternos foram semelhantes entre os grupos quanto a: nivel de bloqueio anestésico, consumo de fenilefrina por tempo, incidencias de hipotensáo, hipertensáo, bradicardia, náuseas, vómitos, dispneia, dor e tremores. Os dados conceptuais evidenciaram semelhan-ga entre os grupos quanto a gasometria e a dosagem de lactato nos vasos umbilicais. Todos os recém-nascidos apresentaram pH > 7,2.

Conclusoes: Mantendo-se a pressáo arterial com infusáo profilática continua de fenilefrina, a incidencia de eventos adversos maternos e as condigoes de nascimento conceptuais náo diferem quando a raquianestesia é realizada com 12 mg ou 8 mg de bupivacaina hiperbárica.

Unitermos: ANESTESIA: Obstétrica; ANESTÉSICOS: Local, bupivacaina; CIRURGIA: Cesárea; COMPLICAQÓES; DROGAS: Fenilefrina; TÉCNICAS ANESTÉSICAS: Regional, subaracnóidea.

[Rev Bras Anestesiol 2011;61(4): 409-424] ©Elsevier Editora Ltda.

INTRODUQÁO

A raquianestesia é a técnica anestésica mais utilizada em todo o mundo para cesariana 1-4. A hipotensáo arterial, entretanto, persiste como a principal complicagáo relacionada

Recebido do Hospital Mater Dei, Belo Horizonte, MG, Brasil.

1. Intensivista - AMIB; Coordenador do Servigo de Anestesiologia do Hospital Mater Dei

2. Professor Titular da Disciplina de Anestesiologia, Dor e Terapia Intensiva da Escola Pau-lista de Medicnia da Universidade Federal Estadual Paulista, EPM-UNIFESP

3. Professora Adjunta da Disciplina de Anestesiologia, Dor e Terapia Intensiva da EPM-UNIFESP

4. Professor Assistente da Disciplina de Anestesiologia, Dor e Terapia Intensiva da EPM-

UNIFESP

Submetido em 12 de agosto de 2010.

Aprovado para publicagäo em 28 de dezembro de 2010.

Correspondéncia para:

Dr. Vinicius Pereira de Souza

Rua Araguari, 1331/1401

Santo Agostinho

30190111 - Belo Horizonte, MG, Brasil

E-mail: vinicius. ps@terra. com. br

com essa técnica 5-7, associando-se vários eventos adversos maternos, como náuseas, vómitos, dispneia e desconforto; e conceptuais, como acidose e sofrimento fetal, dano neuroló-gico e morte 8-9.

Várias estratégias sáo utilizadas visando a prevengáo da hipotensáo arterial relacionada a raquianestesia, des-tacando-se a redugáo da massa de anestésico local e a infusáo continua profilática de fenilefrina. A adigáo de analgésicos opioides lipossolúveis á raquianestesia permitiu reduzir a massa de anestésico local administrada 10, além da incidencia, gravidade e duragáo da hipotensáo arterial, o consumo de vasopressores e a duragáo de bloqueio motor 11-16. Já a infusáo de fenilefrina mostra-se segura e eficaz, náo apresentando os riscos de bloqueio anestésico insuficiente, decorrentes da diminuigáo da massa de anestésico local 17"19.

Este estudo teve por objetivo avaliar, comparativamente, os efeitos da infusáo continua profilática de fenilefrina sobre os resultados maternos e conceptuais, na hipótese de duas massas diferentes de anestésico local habitualmente administradas em raquianestesia para cesariana eletiva.

MÉTODO

Após a aprovagao dos Conselhos de Ética do Hospital Mater Dei em Belo Horizonte/MG e da UNIFESP em Sao Paulo/ SP e da assinatura do termo de consentimento livre e esclarecido pelas pacientes, realizou-se um ensaio clínico, prospectivo, nao aleatório, com 60 gestantes a termo (gestagao com mais de 37 semanas), estado físico I e II pela Sociedade Americana de Anestesiologia (ASA), admitidas para cirurgia de cesariana eletiva.

Consistiram em critérios de exclusao: obesidade com índice de massa corpórea maior que 30 kg.m-2; história de pré-eclampsia e/ou hipertensao arterial prévia; presenga de doengas cardíacas ou cerebrovasculares; rotura da bolsa amniótica; presenga de sinais indicativos de início de traba-lho de parto e situagoes envolvendo contraindicagoes para a realizagao de anestesia subaracnóidea.

As pacientes foram distribuídas em dois grupos, G12 e G8, dependendo da dose de bupivacaína hiperbárica injetada na raquianestesia.

A monitoragao incluiu cardioscopia, oximetria de pulso e pressao arterial nao invasiva. A venóclise foi realizada com cateter intravascular 18G. Sondagem vesical de demora a critério da equipe cirúrgica.

Todas as pacientes receberam expansao volemica com solugao de lactato de Ringer na dose de 10 mL.kg-1, administrada 10 a 15 minutos antes da realizagao do bloqueio anestésico, com volume total de 1.000 mL até o nascimento.

A raquianestesia foi realizada com a paciente em posigao sentada, pungao entre a segunda e a terceira vértebras lom-bares, com agulha 27G, ponta de lápis. Após a pungao, a paciente foi posicionada em decúbito dorsal com desvio uterino para a esquerda por meio de coxim posicionado abaixo do quadril direito.

No grupo G12, foram injetados 12 mg de bupivacaína hiperbárica e no grupo G8, 8 mg. Em ambos os grupos foram acrescentados 5 ^g de sufentanil e 100 ^g de morfina a solugao anestésica. A velocidade de injegao foi de 1 mL a cada 10 segundos.

A pressao arterial foi obtida por meio de método oscilomé-trico, com manguito de pressao colocado no brago esquerdo. A pressao inicial, considerada basal, foi obtida após a entrada da paciente na sala de cirurgia, em decúbito dorsal, sem co-xim abaixo do quadril. Após o bloqueio do neuroeixo, aferiu-se a pressao arterial automaticamente, a cada 3 minutos, até o nascimento.

A infusao contínua de fenilefrina foi realizada em bomba de seringa iniciada imediatamente após a raquianestesia. A velocidade de infusao inicial de fenilefrina foi de 100 ^g.min-1, seguida de ajustes para manter a pressao arterial da paciente nos valores obtidos antes da realizagao do bloqueio. A infu-sao do vasopressor foi interrompida após extragao fetal, ime-diatamente após o pingamento do cordao umbilical.

Em caso de queda da pressao arterial abaixo de 10% da pressao inicial, administrou-se bolus de 50 ^g de fenilefri-na. A hipotensao arterial foi definida como redugao além de 20% na pressao arterial sistólica inicial.

A hipertensao arterial, por sua vez, foi definida como aumento da pressao arterial sistólica acima de 20% da pressao inicial. Na presenga de hipertensao interrompia-se a infusao de fenilefrina, reiniciando-a imediatamente após a primeira medida pressórica, que indicava o retorno da pressao arterial a seu nível basal.

A bradicardia foi definida como redugao da frequen-cia cardíaca abaixo de 50 bpm. Quando a bradicardia era acompanhada de pressao arterial normal e/ou hipertensao, interrompia-se a infusao de fenilefrina. Se a bradicardia fosse acompanhada de hipotensao arterial, administrava-se 1,0 mg de atropina por via venosa.

Em caso de queixa de dor e desconforto pela paciente, em qualquer momento do ato cirúrgico, administrava-se bolus por via venosa de 10 ^g de sufentanil, associado a cetamina 0,2 mg.kg-1.

Imediatamente após o nascimento, realizava-se o duplo pingamento de um segmento de 10 a 15 cm de cordao umbilical para a coleta de amostra de sangue da veia e da arté-ria umbilical do concepto para a realizagao de gasometria e dosagem de lactato, em seringa heparinizada. As amostras foram examinadas em até 60 minutos após a coleta.

O processo de anestesia previu níveis de bloqueio anestésico sensitivo, obtidos cinco e 10 minutos após a realizagao do bloqueio subaracnóideo, em ambas as linhas axilares médias, por meio de pinprick-test.

Os intervalos de tempo registrados durante a anestesia foram: tempo entre o término da realizagao do bloqueio subaracnóideo e o nascimento em minutos; tempo entre a uteroto-mia e o nascimento em segundos; e tempo entre o término da realizagao do bloqueio anestésico e o término da cesariana em minutos.

Registrou-se a massa total infundida de vasopressor, o número de episódios de hipotensao, hipertensao arterial e bradicardia; a necessidade de administragao de atropina; os eventos adversos maternos, como náuseas, vomitos, disp-neia, dor, desconforto e tremores; e a necessidade de com-plementagao anestésica até o final da cesariana.

Analisaram-se, nos recém-nascidos, os seguintes dados: peso, índice de Apgar no primeiro e quinto minutos, gasometria e dosagem de lactato de artéria e veia umbilicais.

A análise estatística empregada para as variáveis numéricas continuas foi o teste t de Student, estudando-se a homogeneidade dos grupos em relagao a idade, idade gestacional, peso, pressao arterial sistólica inicial e frequencia cardíaca inicial, volume e massa total de vasopressores administradas, bem como os valores gasométricos e a dosagem de lactato dos vasos umbilicais. Os tempos entre o bloqueio anestésico e o nascimento e entre a uterotomia e o nascimento foram avaliados pelo teste Mann-Whitney. Considerou-se um nível de significancia de 0,05%.

As diferengas entre os grupos em relagao ao nível de bloqueio anestésico sensitivo foram analisadas pelo teste Qui-quadrado de tendencia. A incidencia de eventos adversos maternos e a necessidade de administragao de atropina foram analisadas pelo teste exato de Fisher e pelo teste Qui-quadrado.

Os softwares de estatística utilizados foram Excel 97-2003 e SPSS 16.0.

Considerando o nível de significancia de 5%, poder de 80% e o objetivo primário de controle da pressao arterial pela ocorréncia de náuseas e vomitos, calculou-se o tamanho amostral em 23 pacientes em cada grupo. Foram estudadas 30 pacientes em cada grupo, em virtude de a coleta de dados ter sido realizada previamente ao cálculo amostral.

RESULTADOS

As principais indicagoes para a realizagao de cesariana es-tao apresentadas na Tabela I. Com relagao ao estado físico, observou-se que nos grupos G12 e G8, 73,3% e 86,7% das pacientes eram ASA I, e 22,7% e 13,3% eram ASA II pacientes, respectivamente.

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Tabela I - Indicagoes de Cesariana

G12 (n) G8 (n)

Cesariana prévia 13 15

Desproporgao cefalopélvica 11 9

Pedido materno 4 2

Outras* 2 4

Dermátomo

□ g12 □ g8

Figura 1 - Nível Sensitivo de Bloqueio Anestésico após 5 minutos da injegáo subaracnoidea nos grupos G12e G8. G12: Grupo 12 mg; G8: Grupo 8 mg.

Valores apresentados como número de pacientes.

*Outras: Miomatose uterina, oligo-hidramnio, macrossomia fetal

Tabela II - Características das Pacientes

G12 G8 p

Idade (anos) 31 ± 6,2 (16-43) 31,1 ± 5,8 (23-43) 0,931

Peso (kg) 73,3 ± 10 (60-95) 74,5 ± 11,8 (54-104) 0,672

Altura (cm) 161,1 ± 20 (160-176) 163 ± 5,1 (153-171) 0,628

Idade gestacional (semanas) 38,6 ± 0,9 38,3 ± 0,7 0,154

Pressao sistólica basal (mmHg) 122,3 ± 10,3 (105-42) 121,7 ± 10,6 (100-141) 0,825

Frequéncia cardíaca basal (bpm) 87,3 ± 12,3 (64-108) 87,9 ± 13,9 (60-115) 0,875

Valores apresentados como média ± desvio-padráo e (valor mínimo - valor máximo).

Os grupos mostraram-se homogéneos quanto as características das pacientes. (Tabela II).

Nao houve diferenga entre os grupos com relagáo aos ní-veis sensitivos de bloqueio anestésico, após 5 e 10 minutos da injegáo subaracnoidea (Figuras 1 e 2). Nos dois grupos, a maior frequéncia do nível do bloqueio sensitivo, após 5 e 10 minutos da injegáo de anestésico local, foi em T6 e T4, respectivamente.

As médias para o tempo de bloqueio-nascimento foram de 23,3 minutos para G12 e 18,6 minutos para G8 (Tabela III), com diferenga significativa entre grupos (p = 0,0009) (Figura 3). O tempo de uterotomia-nascimento nao apre-sentou diferenga significativa entre os grupos (p = 0,695), registrando-se médias de 75,0 segundos para o grupo G12 e 73,9 segundos para o G8. A duragao total do procedimento, medida pelo tempo de bloqueio-término da cirurgia, apresen-tou médias de 72,44 minutos e 67,33 minutos nos G12 e G8, respectivamente, sem diferenga significativa entre os grupos (p = 0,171) (Tabela III).

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Dermátomo

□ G12 □ G8

Figura 2 - Nível Sensitivo de Bloqueio Anestésico, após 10 minutos da injegao subaracnoidea nos grupos G12 e G8. G12: Grupo 12 mg; G8: Grupo 8 mg.

A massa total de fenilefrina administrada apresentou dife-renga significativa (p = 0,0023) entre G12 (média de 1.024,3 ^g) e G8 (média de 794,2 ^g). Comparando-se a relagao entre massa total de fenilefrina administrada pelo tempo de anes-tesia-nascimento (tempo de infusao de fenilefrina), nao foram evidenciadas diferengas entre os grupos (p = 0,9753). Nao houve diferenga entre os grupos com relagao as incidencias de hipotensao e hipertensao arterial. A incidencia de bradi-cardia foi igual em ambos os grupos e nao houve necessida-de de administragao de atropina (Tabela IV).

O maior e o menor valor de pressao arterial sistólica e de frequencia cardíaca registrados nao foram diferentes entre os grupos (Tabela V). Nao houve diferenga em relagao as evolu-goes dos valores da pressao arterial e da frequencia cardíaca entre os grupos (Figura 3).

Nao houve diferenga na incidencia de eventos adversos maternos entre os grupos (Tabela VI). Apenas uma paciente (3,3%) do G12 apresentou náuseas e uma paciente (3,3%) do G8 apresentou dispneia. Nenhuma paciente queixou-se de dor, desconforto ou apresentou vomitos até o final da ope-ragao. Nao foi necessária complementagao anestésica nas pacientes estudadas.

Os dados dos recém-nascidos em ambos os grupos mos-traram-se homogéneos (Tabela VII). Apenas um recém-nas-

Evoluçâo da Pressao Arterial Sistólica e da Frequência cardiaca ao lonqo do tempo

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PAS G12

6 9 12 15 18 21 24 Tempo (mim) PAS G8 —A—FC G12 —0—FC G8

Figura 3 - Evolugáo das Médias da Pressáo Arterial Sistólica (mmHg) e da frequencia cardíaca (bpm) ao longo do tempo (min) no G12 e G8. PAS: Pressao arterial sistólica; FC: Frequencia cardíaca.

Tabela III - Tempos Anestésico-Cirúrgicos

G12 G8 p

Bloqueio-nascimento (minutos) 23,3 ± 5,6 18,6 ± 4,7 0,0009*

Uterotomia-nascimento (segundos) 75 ± 53,6 73,9 ± 60,8 0,695

Bloqueio-término da cirurgia (minutos) 72,44 ± 15,70 67,33 ± 12,74 0,17

Valores apresentados como média ± desvio-padráo. *Estatística significativa: p < 0,05

Tabela IV - Consumo de Vasopressores e Variáveis Hemodinâmicas

Massa total de fenilefrina administrada (^g) Massa de fenilefrina/tempo de infusáo (^g.min-1) Incidencia de Hipotensáo Arterial** Incidencia de Hipertensáo Arterial** Bradicardia**

Administraçâo de atropina**_

1.024,3 ± 277,4 44,06 ± 6,63 7 (23%) 11 (33,6%) 4 (13,4%) 0 (0%)

794,4 ± 281,1 44,18 ± 13,97 2 (6,6%) 5 (16,7%) 5 (16,7%) 0 (0%)

0,0023* 0,957 0,145 0,144 0,735 1

Valores apresentados como média ± desvio-padrao para o consumo de fenilefrina. Os outros dados (**) sao apresentados como n e (%). * Estatística significativa: p < 0,05

Tabela V - Valores de Pressao Arterial e Frequencia Cardíaca Máxima e Mínima nos Grupos G12 e G8

G12 G8 p

Pressao arterial sistólica

Máxima (mmHg) 140,4 ± 10,8 (122-167) 137,2 ± 11,0 (115-155) 0,25

Mínima (mmHg) 108,5 ± 12,0 (77-140) 112,7 ± 10,3 (91-134) 0,15

Frequencia cardíaca

Máxima (bpm) 90,1 ± 11,8 (66-115) 89,6 ± 13,1 (66-112) 0,88

Mínima (bpm) 60,7 ± 7,9 (48-75) 60,8 ± 10,2 (46-89) 0,98

Os valores sáo apresentados como média ± desvio-padráo (máximo e mínimo).

Tabela VI - Eventos Maternos Adversos

Gj2_Ga_P

Náuseas 1 (3,3%) 0 (0%) 1

Vomitos 0 (0%) 0 (0%) 1

Dor 0 (0%) 0 (0%) 1

Dispneia 0 (0%) 1 (3,3%) 1

Tremores 4 (13,3%) 6 (20%) 0,729

Os valores apresentados sao os números de episódios (percentagem).

Tabela VII - Características dos Recém-Nascidos

G 12 G 8 p

Peso (g) 3.137,6 ± 352,9 3.206,1 ± 405,2 0,488

APGAR 1 min < 7 1 (3,3%)* 0 (0%)* 1

APGAR 5 min <7 0 (0%)* 0 (0%)* 1

Gasometria Artéria Umbilical:

pH 7,33 ± 0,04 7,33 ± 0,04 0,839

pCO2 (mmHg) 45,8 ± 8,1 45,9 ± 6,9 0,925

Bicarbonato (mmol.L-1) 24 ± 4,5 23,8 ± 2,0 0,819

BE (mmol.L-1) -1,2 ± 1,4 -1,3 ± 1,7 0,941

Lactato arterial (mmol.L-1) 1,8 ± 0,4 1,9 ± 0,5 0,781

Gasometria Veia Umbilical:

pH 7,35 ± 0,04 7,35 ± 0,05 0,839

pCO2 (mmHg) 42,7 ± 6,1 42,7 ± 6,9 0,955

Bicarbonato (mmol.L-1) 23,6 ± 3,4 22,8 ± 1 ,9 0,275

BE (mmol.L-1) -1,7 ± 1,3 -2,1 ± 1,7 0,412

Lactato venoso (mmol.L-1) 1,8 ± 0,4 1,9 ± 0,6 0,361

Acidose fetal (pH < 7,2) 0 (0%)* 0 (0%)* 1

* Os valores sao apresentados como número e percentagem de pacientes.

cido do G12 apresentou Apgar igual a trés no primeiro minuto. Todos os outros apresentaram pontuagao superior a sete no Apgar do primeiro minuto. Aos 5 minutos, a pontuagao desse índice foi maior que sete em todos os recém-nascidos.

As médias de tempo entre a coleta de sangue da veia e da artéria umbilical e a realizagao dos exames gasométricos e dosagens de lactato foram de 20,29 minutos e 19,71 minutos para G12 e G8, respectivamente. Os maiores intervalos de tempo entre a coleta de sangue e a realizagao dos exames foram de 42 e 43 minutos para G12 e G8, respectivamente.

DISCUSSAO

O estudo questiona os benefícios da estratégia de redugao da massa de anestésico local em raquianestesia para cesa-riana eletiva sobre os resultados maternos e conceptuais, na hipótese de infusao contínua e profilática de fenilefrina.

Na prática clínica, a escolha da massa de anestésico local subaracnoidea administrada é realizada de maneira intuitiva pelos profissionais, de acordo com a agilidade e a experiéncia das equipes cirúrgicas, considerando a maior dispersao dos anestésicos em parturientes. Optou-se por administrar maior e menor massa de anestésico, 12 mg ou 8 mg de bupivacaí-

na hiperbárica, para aquelas equipes cirúrgicas previamente conhecidas com maior e menor tempo cirúrgico, respectivamente. A homogeneidade de características das amostras e dos grupos estudados diminuiu o viés decorrente da selegao nao aleatória dos grupos.

A opgao pela injegao subaracnoidea de 12 mg de bupi-vacaína hiperbárica justifica-se por ser uma dose tradicio-nalmente administrada em raquianestesia para cesariana na prática clínica. Já a dose de 8 mg, associada a opioides lipossolúveis, representa uma redugao de 33,33% da massa total de bupivacaína administrada e pode ser utilizada com seguranga para a realizagao de raquianestesia para cesaria-na 12 20. Publicagao recente 21 relata que doses entre 5 mg e 7 mg de bupivacaína hiperbárica, associadas aos opioides, podem ser utilizadas apenas por meio de um bloqueio combinado, sendo obrigatória a presenga do cateter peridural para a complementagao analgésica. A dose de 8 mg utilizada em nosso estudo encontra-se acima do limite mínimo preconizado pelos autores, podendo ser administrada com seguranga em raquianestesia com pungao única, sem haver necessida-de de bloqueio combinado. Apenas um estudo publicado por Bryson e col.. 22 evidencia a seguranga da utilizagao de doses de 4,5 mg de bupivacaína isobárica, associadas a 50 ^g de fentanil e 200 ^g de morfina em raquianestesia para cesa-

riana. Torna-se necessária, no entanto, a repetigao desses dados para alterar condutas na prática clínica.

A associagao de opioides lipossolúveis ao anestésico local em raquianestesia para cesariana promove melhora da qualidade do bloqueio anestésico, com a redugao eficaz do componente visceral da dor durante a cesariana 23. Doses subaracnoideas maiores de 5 ^g de sufentanil associam-se a melhora na qualidade do bloqueio anestésico, mas au-mentam significantemente a incidencia de efeitos colaterais, como, por exemplo, o prurido 23 24. A associagao de sufentanil em solugao de raquianestesia reduz o período de latencia do bloqueio anestésico, melhora a qualidade no período intrao-peratório e proporciona analgesia no pós-operatório imediato com duragao em torno de 6 horas 25.

Foi associada morfina a solugao anestésica de raquianestesia para proporcionar analgesia de maior duragao no período pós-operatório imediato. Tratando-se de opioide hi-drossolúvel, a morfina apresenta início de agao mais lento que os opioides lipossolúveis e maior duragao de agao 10. Foi padronizada a dose de 100 ^g de morfina, porque os estudos relatam que doses maiores nao adicionam benefícios e estao associadas a maior incidencia de prurido 26-28.

Uma das principais mudangas de conceitos relacionadas a administragao de raquianestesia para cesariana está relacionada a prevengao da hipotensao arterial pós-raquianestesia, por meio da infusao profilática de fármacos alfa1-adrenérgi-cos, objetivando mínimas redugoes de pressao arterial. A administragao profilática contínua de fenilefrina reduz a incidencia de náuseas e vomitos maternos, resultando em maior pH do sangue colhido em vasos umbilicais 17. Optou-se, neste estudo, pela infusao profilática de fenilefrina para controle hemodinamico, objetivando-se quedas mínimas de pressao arterial.

Várias publicagoes na literatura médica demonstraram os benefícios da redugao da massa de anestésico local em ra-quianestesia para cesariana, com diminuigao das incidencias de hipotensao arterial, náuseas e vomitos maternos, além do menor consumo de vasopressores 12,13 16,22 29. Esses estudos adotaram, porém, estratégia terapeutica de administragao de vasopressores, diante da redugao maior ou igual a 30% da pressao arterial sistólica inicial ou diminuigao da pressao arterial sistólica abaixo de 90 mmHg, após a realizagao da raquianestesia. Tal estratégia, entretanto, já nao representa o "padrao ouro" de raquianestesia para cesariana.

Por outro lado, os estudos que utilizaram a estratégia pro-filática de fenilefrina para controle pressórico sao escassos nesse contexto de redugao da massa de anestésico local, tendo em vista que seu foco encontrava-se basicamente na perspectiva de comparagao de modos diferentes de admi-nistragao de fenilefrina. Assim, adotava-se uma dose fixa de anestésico local, variando o modo de administragao desse vasopressor 19.

No presente estudo, os níveis sensitivos de bloqueio anestésico foram medidos após 5 e 10 minutos da injegao subarac-noidea e sugerem igual dispersao dos anestésicos em ambos os grupos estudados. Após 10 minutos de bloqueio anestési-

co, o nível sensitivo atingiu T6 nos dois grupos. Esse nível de bloqueio é considerado seguro para o início da cirurgia 30.

O nível de bloqueio simpático pode atingir até quatro dermá-tomos acima do nível sensitivo de bloqueio 31. O nível de bloqueio evidenciado após 10 minutos (T6 em ambos os grupos) de realizaçao da raquianestesia causa bloqueio de pratica-mente toda a cadeia simpática dos dois grupos. A dispersao de anestésicos locais no espaço subaracnóideo pode estender-se por até 20 a 2б minutos, após a injeçao subaracnoidea 31. Considerando o nível do bloqueio aos 10 minutos, provavelmente a dispersao adicional do anestésico nao influenciou a incidência de hipotensao arterial e o consumo de vasopressores.

O consumo total de fenilefrina foi maior no G12 do que no G8. Tal diferença justifica-se pela escolha nao aleatória dos grupos estudados, e maior massa de anestésico local foi administrada para aquelas equipes cirúrgicas que apresentavam maior tempo cirúrgico. O grupo da massa de 12 mg de bupivacaína hi-perbárica apresentou maior intervalo de tempo entre a realizaçao do bloqueio e a extraçao do concepto e, por conseguinte, maior tempo de infusao e maior consumo total de fenilefrina.

A diferença em relaçao ao consumo total de fenilefrina nao pode ser atribuída às diferenças de nível sensitivo de bloqueio anestésico, em virtude da homogeneidade dos níveis de blo-queio anestésico, que nao apresentaram diferença entre os grupos.

O maior consumo total de fenilefrina foi de 1.024 ^g no G12 e mostrou-se seguro para a utilizaçao em raquianestesia para cesariana. A administraçao de massa total de fenilefrina de até 1.б00 ^g já foi descrita na literatura como nao causadora de efeitos adversos para a mae e para o feto 17. Atualmente, a fenilefrina é um fármaco de primeira linha para a prevençao da hipotensao arterial pós-raquianestesia 32.

A variaçao da massa de anestésico local administrada nao apresentou impacto para a reduçao ou o aumento do consumo de vasopressor por unidade de tempo. Ajustando-se o consumo total de fenilefrina pelo tempo de infusao do fármaco (^g.min-1) nao foram evidenciadas diferenças entre os grupos estudados, confirmando que o maior consumo total observado no G12 foi decorrente do maior tempo de infusao. Os estudos publicados, porém, evidenciam a reduçao do consumo de vasopressores com a diminuiçao da massa de anestésico local 12"16. A diferença em relaçao aos resultados obtidos com nosso estudo pode ser explicada pelo fato de esses autores terem adotado uma estratégia terapêutica de administraçao de vasopressores.

Várias publicaçбes fixam a dose de anestésico local e ava-liam as diferentes doses e modos de administraçao de fenile-frina, isoladamente ou em conjunto com outros fármacos vasopressores, analisando a segurança e os efeitos adversos de sua administraçao 17 1933. Recentemente, os efeitos da infusao profilática de fenilefrina foram analisados em 80 pacientes sub-metidas à raquianestesia para cesariana com 10 mg ou 7 mg de bupivacaína isobárica associadas a 4 mcg de sufentanil 34. A velocidade de infusao de fenilefrina mostrou-se inferior à velocidade de infusao deste estudo. Os autores evidenciaram que as menores alteraçбes hemodinâmicas estao associadas

a administragao de baixas doses de anestésico local, concomi-tantemente a infusao contínua de fenilefrina.

A incidéncia de hipotensao arterial encontrada com a utili-zagao do protocolo de administragao profilática de fenilefrina está em consonancia com o estudo realizado por Ngan Kee e col. 17, quando se observou incidéncia de hipotensao arterial de 16%, definindo hipotensao como queda superior a 20% da pressao arterial sistólica basal, na vigéncia de 10 mg de bupi-vacaína subaracnoidea.

Embora tenhamos registrado baixa incidéncia de hipotensao arterial no G8, estudo publicado pelo mesmo grupo de Ngan Kee e col. 19 evidenciou incidéncia ainda menor de hipotensao arterial, 1,2%. Tal diferenga pode ser explicada pela infusao de um grande volume de cristaloide (2.000 mL de solugao de lactato de Ringer), previamente a administragao do bloqueio anestésico neste artigo citado, em contrapartida com o volume máximo de 1.000 mL de lactato de Ringer administrado até a extragao fetal neste estudo.

Os principais efeitos adversos maternos causados pela in-fusao contínua de fenilefrina foram hipertensao arterial e bra-dicardia. A incidéncia média de hipertensao arterial em ambos os grupos foi inferior aos resultados relatados pela literatura, cuja incidéncia pode atingir 47%, sem causar repercussoes maternas e neonatais negativas 19.

Na literatura, a incidéncia de bradicardia com infusao de fenilefrina chega a 5% 1535, podendo necessitar de administra-gao de atropina. A bradicardia pode resultar do aumento da re-sisténcia vascular periférica causado pela fenilefrina, que leva ao aumento de pós-carga do ventrículo esquerdo e a redugao da frequéncia cardíaca 36. O presente estudo evidenciou maior incidéncia de bradicardia no grupo de 8 mg (16,7%). Ngan Kee e col. 19 relatam incidéncia de bradicardia de 24,8% de bradicardia, diante da infusao de até 100 ^g.min-1 de fenilefrina.

Nossos resultados mostram que os episódios de bradicar-dia nao foram acompanhados de repercussoes hemodina-micas (hipotensao) e nao necessitaram de administragao de atropina, sendo tratados com a interrupgao da infusao de va-sopressor. Esses dados também estao em consonancia com a literatura 15 19 35. Outras arritmias cardíacas, como por exemplo o bigeminismo ventricular, nao foram aqui observadas 37.

A incidéncia de eventos adversos maternos foi mínima; apenas 1/30 (3,3%) apresentou um episódio de náuseas no grupo de maior massa de anestésico local. Esse episódio de náuseas ocorreu em concomitancia com um episódio de hipotensao arterial, registrando-se redugao da pressao arterial sistólica de 115 mmHg para 90 mmHg. A incidéncia de náuseas registrada em ambos os grupos foi menor do que a relatada na literatura, cuja incidéncia pode chegar a 16% 17.

As baixas incidéncias de náuseas e vomitos evidenciadas decorrem da associagao do controle pressórico estrito com opioides lipossolúveis a solugao de raquianestesia. Cerca de 80% dos episódios intraoperatórios de náuseas e vomitos decorrem de hipotensao arterial. Outras causas de náuseas e vomitos no intraoperatório sao estímulos cirúrgicos, como a manipulagao e a tragao do peritonio e de órgaos intra-abdomi-nais. A adigao de analgésicos subaracnóideos a solugao de anestésicos locais melhora a qualidade do bloqueio anestésico

e reduz a incidéncia de náuseas e vomitos intraoperatórios 23. Estratégias nao profiláticas de controle pressórico pós-raquia-nestesia apresentam maior incidéncia de eventos adversos maternos como náuseas e vomitos, que podem acometer até 40% das pacientes 12,13,36,38.

Nenhuma das pacientes queixou-se de dor e/ou desconforto durante a realizagao do procedimento cirúrgico, tampouco necessitou de complementagao anestésica, o que evidencia a seguranga na utilizagao da dose de 8 mg de bupivacaína hiperbárica em raquianestesia com pungao única, associada a 5 ^g de sufentanil e 100 ^g de morfina, para cesarianas com duragao média de 67 minutos. Massas entre 5 mg e 7 mg de bupivacaína hiperbárica podem ser administradas para cesa-rianas com duragao entre de 50 e 70 minutos 21. Recomendase, no entanto, a realizagao de um bloqueio combinado para tais doses 21.

Os resultados conceptuais nao apresentaram diferenga significativa diante da redugao da massa de 12 mg para 8 mg. Apenas um recém-nascido no grupo de 12 mg apresentou pontuagao 3 no índice de Apgar no primeiro minuto. O tempo de uterotomia-nascimento dessa cesárea foi de 5 minutos e 33 segundos, o que resultou em maior período de isquemia, justificando a baixa pontuagao inicial. O pH da artéria e da veia umbilical desse concepto, contudo, foi superior a 7,20, e a pontuagao no índice de Apgar no quinto minuto foi de 9, sem evidéncia de sofrimento fetal.

As médias registradas de pH arterial e venoso umbilicais foram de 7,33 e 7,35 em ambos os grupos estudados. Esses valores encontram-se em níveis mais elevados do que outros resultados obtidos na literatura 17 e confrontam a metanálise publicada por Reynolds e Seed 39, em que a raquianestesia para cesariana estaria associada a piora do estado ácido-base fetal, quando se comparam as anestesias peridural e geral. Os autores avaliaram 27 estudos e concluíram que as pacientes submetidas a raquianestesia apresentaram pH inferior ao pH das pacientes submetidas a anestesia geral e peridural, sendo tal diferenga de 0,015, incluindo estudos publicados desde a década de 1960. A raquianestesia realizada nessa época apresentava conceitos e estratégias diferentes daqueles que hoje se apresentam e a administragao de efedrina poderia ser a responsável por essas diferengas de resultados. A efedrina, ultrapassando a barreira placentária, aumentaria o metabolismo fetal e a liberagao de catecolaminas 9 40-42. Há grande transferéncia placentária de efedrina em comparagao com a fenilefrina, apresentando repercussoes para o feto, com aumento significativo na concentragao de catecolaminas circulantes 43. Evidencia-se a seguranga da utilizagao de fenilefri-na em raquianestesia para cesariana eletiva com resultados confirmados por vários artigos clínicos e experimentais 44 47. A utilizagao de fármacos alfa1-adrenérgicos mostrou-se segura e eficaz, sendo que o pH da artéria e da veia umbilicais foi de 7,33 e 7,35 nos grupos G12 e G8, respectivamente. Esse pH revela boas condigoes de nascimento, relacionadas com raquianestesia, assim como seguranga na administragao de fenilefrina sobre o estado ácido-base fetal 32.

A colheita do sangue da veia e da artéria umbilical efe-tuou-se por meio da técnica de duplo pingamento do cordao

umbilical, em seringa previamente heparinizada, e todas as amostras foram analisadas com menos de 60 minutos após a colheita. O Colégio Americano de Ginecologia e Obstetrícia recomenda a análise das amostras em até 60 minutos após a coleta em seringa heparinizada 48. Estudos realizados sobre os efeitos do tempo de exame sobre os resultados da gasometria da artéria e da veia do cordao umbilical evidenciaram que, após 60 minutos da colheita da amostra, os valores de pH nao se alteraram 49; entretanto, os valores de pCO2 diminu-íram significativamente, enquanto os de pO2 aumentaram. O estudo questiona, por fim, a eficácia da utilizaçao da estratégia de reduçao da massa de anestésico local sobre os resultados maternos e conceptuais, em pacientes submetidas à raquianestesia para cesariana eletiva, adotando-se controle estrito da pressao arterial com a infusao de fenilefrina. A prevençao da hipotensao arterial com a utilizaçao de uma estratégia profilá-tica de infusao de vasopressores substitui os efeitos benéficos da reduçao da massa de anestésico local sobre os resultados maternos e conceptuais.

Este estudo, porém, nao avaliou eventuais diferenças entre os resultados maternos que poderiam ter sido observadas após a extraçao fetal, como, por exemplo, o tempo de regres-sao do bloqueio motor, a utilizaçao de fármacos uterotónicos e a analgesia pós-operatória; esses dados também estariam relacionados com a satisfaçao materna 22 5G.

Conclui-se que, em pacientes submetidas à raquianestesia para cesariana eletiva com controle pressórico estrito com fe-nilefrina, a variaçao da massa de bupivacaína hiperbárica de 12 mg para В mg nao está associada a diferenças na incidên-cia de eventos adversos maternos, na qualidade do bloqueio anestésico até o término da operaçao e nas cond^es de nas-cimento conceptuais.

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Resumen: Souza VP, Amaral JLG, Tardelli MA, Yamashita AM -Efectos de la Infusión Continua Profiláctica de Fenilefrina sobre la Estrategia de Reducción de la Masa de Anestésico Local en Pacientes Sometidas a la Raquianestesia para Cesárea.

Justificativa y objetivos: La reducción de la masa del anestésico local minimiza los efectos de la hipotensión arterial postraquianestesia para cesárea, y reduce la incidencia de eventos adversos maternos preservando el bienestar fetal, pero puede conllevar a una anestesia insuficiente. La hipotensión asociada a las mayores masas de anestésico subaracnóideo puede ser controlada con una infusión continua profiláctica de fenilefrina. Fueron evaluados los efectos de la infusión continua profiláctica de fenilefrina para el control presórico sobre los resultados maternos y conceptuales, en cesáreas con diferentes dosis de bupivacaína hiperbárica en la raquianestesia.

Método: Se realizó un ensayo clínico prospectivo, no aleatorio con 60 embarazadas a término, admitidas para la cesárea electiva. Las pacientes fueron ubicadas en dos grupos, en dependencia de la dosis de bupivacaína hiperbárica administrada en la raquianestesia, 12 u 8 mg, añadida de 5 ^g de sufentanil y 100 ^g de morfina. Se realizó la hidratación con 10 mL.kg-1 de solución de Ringer con lactato antes del bloqueo. Inmediatamente se inició la infusión continua de 100 ^g. min-1 de fenilefrina, manteniendo la presión arterial en los valores basales. Fueron evaluados: nivel de bloqueo anestésico, consumo de vasopresores, incidencia de eventos adversos maternos y condiciones del recién nacido.

Resultados: Los datos maternos fueron similares entre los grupos en cuanto al nivel de bloqueo anestésico, consumo de fenilefrina por tiempo, incidencias de hipotensión, bradicardia, náuseas, vómitos, disnea, dolor y temblores. Los datos conceptuales arrojaron una similitud entre los grupos en cuanto a la gasometría y a la dosificación de lactato en los vasos umbilicales. Todos los recién nacidos presentaron un pH > 7,2.

Conclusiones: Manteniendo la presión arterial con infusión profiláctica continua de fenilefrina, la incidencia de eventos adversos maternos y las condiciones de nacimiento conceptuales no son diferentes cuando la raquianestesia se hace con 12 mg u 8 mg de bupivacaína hiperbárica.

Descriptores: ANESTESIA: Obstétrica; ANESTÉSICOS: Local, bupivacaína; CIRUGÍA: Cesárea; COMPLICACIONES; FÁRMACOS: fenilefrina; TÉCNICAS ANESTÉSICAS: Regional, subaracnoidea.