Anesth Analg 2004;98:1280-1283
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000108962.37210.69
PEDIATRIC ANESTHESIA
Spinal Anesthesia with Bupivacaine Decreases Cerebral Blood Flow in Former Preterm Infants
Marie-Pierre Bonnet, MD,
Eric Larousse, MD,
Karim Asehnoune, MD, and
Dan Benhamou, MD PhD
From the Département d’Anesthésie Réanimation, Centre Hospitalo-Universitaire de Bicêtre, Kremlin Bicêtre, France
Address correspondence and reprint requests to Dan Benhamou, MD, Department of Anesthesiology and Intensive Care Medicine, CHU de Bicêtre 78, Rue du Général Leclerc F-94275 Kremlin Bicêtre. Address email to mariepierre.bonnet{at}9online.fr
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Abstract
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Spinal anesthesia is commonly used in former preterm infants (FPI). In these patients, hypotension induced by spinal anesthesia may impair cerebral blood flow. We measured cerebral blood flow velocity (CBFV) by transcranial Doppler ultrasound to assess the effect of hypotension induced by spinal anesthesia on cerebral hemodynamics. Twelve FPI scheduled for inguinal hernia repair were operated under spinal anesthesia using 1 mg/kg isobaric 0.5% bupivacaine. Systolic, diastolic, and mean middle cerebral artery CBFV were measured at 5 min before and 5 min and 10 min after spinal anesthesia using a transcranial pulsed Doppler ultrasonography. Arterial blood pressure and heart rate were recorded simultaneously. Cerebral arteries resistance index (RI) was calculated as RI = (peak systolic CBFV – end-diastolic CBFV)/peak systolic CBFV. Diastolic CBFV decreased significantly from 30.0 ± 11.1 cm/s to 20.1 ± 8.4 cm/s at 5 min and to 20.1 ± 7.0 cm/s at 10 min. RI increased significantly from 0.7 ± 0.1 to 0.8 ± 0.1 at 5 min and 10 min. Systolic, diastolic, and mean arterial blood pressures decreased significantly at the same time intervals. We suggest that in FPI, spinal anesthesia induces a decrease in cerebral blood flow related to changes in arterial blood pressure. Whether these changes have deleterious consequences remains to be determined.
IMPLICATIONS: In former preterm infants having spinal anesthesia with bupivacaine, a decrease in cerebral blood flow velocity is displayed by middle cerebral artery transcranial Doppler examination.
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Introduction
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After general anesthesia, former preterm infants (FPI) have a significant anesthetic risk, especially for postoperative apnea (1). The probability of apnea is directly related to a weak central respiratory drive and inversely related to the postconceptual age (2). The incidence of postoperative apnea is less frequent after spinal anesthesia compared with general anesthesia (3). Spinal anesthesia is thus commonly used in FPI for surgery of the lower part of the body such as inguinal hernia repair (4).
The preganglionic sympathetic block secondary to spinal anesthesia induces a decrease in arterial blood pressure (ABP). Dohi et al. (5) have shown that children younger than 5 yr of age have better cardiovascular stability than adults during spinal anesthesia. This is probably related to their smaller lower extremity blood volume and to a less developed sympathetic nervous system.
Several studies have documented that in preterm infants, cerebral blood flow (CBF) autoregulation occurs only within a narrow range of mean ABP (6) or is totally absent (7). Consequently, any change in ABP may have a significant impact on CBF. Transcranial Doppler (TCD) ultrasonography, initially described by Aaslid et al. (8), is a noninvasive technique currently used to measure cerebral blood flow velocities (CBFV) and to evaluate CBF. We conducted a prospective cohort study in FPI to assess the effect of spinal anesthesia and related changes in ABP on cerebral hemodynamics evaluated by TCD echosonography.
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Methods
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Twelve FPI undergoing unilateral inguinal hernia repair were studied prospectively after approval by our ethical committee (CCPPRB, University Hospital Kremlin-Bicêtre, France) and parental consent. Patients were consecutively included in the study from May 2002 to October 2002. Inclusion criteria were ASA physical status I–II, gestational age 
37 wk, postconceptual age 60 wk. Exclusion criteria were central nervous system disease (intracranial hemorrhage or periventricular leukomalacia), cardiac disease, pulmonary sequelae, spinal malformation, and hemostasis disorder.
Patients fasted for 4 h for solids and for 2 h for fluids before anesthesia. IV fluids with dextrose were infused at 4 mL · kg–1 · h–1 starting 2 h before surgery and were maintained until discharge from the recovery room. They received no premedication. Heart rate and arterial blood saturation in oxygen were continuously monitored. ABP was measured every 2.5 min with an automated blood pressure cuff. Normothermia was maintained using a warming blanket.
Spinal anesthesia was performed in the sitting position while the child was held motionless. The usual aseptic precautions were applied. Lumbar puncture was performed at the L4-5 interspace with a pediatric 25-gauge 3.5-cm lumbar puncture needle (Polymedic®, conical-elliptic shaped spinal needle, Bondy, France). When a free flow of cerebrospinal fluid was obtained, a 1-mg/kg dose of 0.5% isobaric bupivacaine was injected over 5 s with a 1-mL syringe. Infants were then placed in supine position.
Middle cerebral artery (MCA) systolic, diastolic and mean CBFV were measured 5 min before (T0) and 5 min (T1) and 10 min after (T2) spinal anesthesia. Systolic, diastolic, and mean ABP and heart rate and arterial oxygen saturation were recorded simultaneously. A TCD ultrasonography (SONOS® 500P; Hewlett Packard, Les Ulis France) was used for CBFV measurements. Position of the probe was adjusted by ultrasound scan. The Circle of Willis was located by ultrasonography and the Doppler Windows cursor was then placed on the M1 part of the MCA to record the CBFV of the MCA in a reproductive manner. The Doppler signal was optimized for clear and accurate determination by adjusting the position of the probe, the scale and the gain of the measurement, and the angle of insonation. The cerebrovascular resistance index (RI) was calculated for each MCA velocity measurement according to the following formula (9): equation
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In the literature, RI has never been compared to other means to measure cerebrovascular resistances. It is a mathematical concept. Its variations in different clinical situations have already been described (10); for example, in hypoxic-ischemic insult, within the first 48 h, several investigators demonstrated a low RI. In cerebral edema, RI decreases during the first 48 h, then, as the cerebral edema continues to develop, RI increases. In general, increasing hydrocephalus is associated with an increase in RI; the index may be normal with stable hydrocephalus. Spectral analysis of arteriovenous malformation shows extremely low RI in the nidus.
The number of patients enrolled in this study was determined by a power analysis based on an expectation of a 25% change in CBFV, with 
= 0, 05 and ß = 0, 20. Each patient was his/her own control. Data were compared using analysis of variance for repeated measured, followed by paired Student’s t-test. Results are reported as mean ± SD. Differences were considered statistically significant at the 5% level. We used Bonferroni correction for multiple comparisons. We performed only 2 comparisons (T0 versus T1 and T0 versus T2) and adjusted P < 0.025 for each comparison to maintain < 0.05.
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Results
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Patients’ demographics are reported in Table 1. Infants were born between 29 and 35 wk of gestation (mean, 32 ± 2 wk). Spinal anesthesia was rapidly effective in each patient and confirmed by the fact that all infants had motor block of the lower limbs within 5 min. Spinal anesthesia was successful and allowed surgery in all patients. No complications were observed during the postoperative period. Mean heart rate did not change significantly at any time. Values of systolic, diastolic, and mean ABP decreased significantly from T0 to T2 (Table 2). Mean ABP decreased significantly from T0 to T1 (Table 2). Diastolic CBFV decreased significantly from T0 to T1 (from 30 ± 11 cm/s to 20 ± 8 cm/s; P < 0.01) and from T0 to T2 (from 30 ± 11 cm/s to 20 ± 7 cm/s; P < 0.01) (Fig. 1). RI increased significantly from T0 to T1 (from 0.7 ± 0.1 to 0.8 ± 0.1; P < 0.01) and from T0 to T2 (from 0.7 ± 0.1 to 0.8 ± 0.1; P < 0.01) (Fig. 2).
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Figure 1. Middle cerebral artery systolic and diastolic velocities (cm/s). *P < 0.01 when compared with "before SA" value. SA = spinal anesthesia; SV = systolic velocity; DV = diastolic velocity.
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Figure 2. Pourcelot’s index (RI = (systolic CBFV – diastolic CBFV)/systolic CBFV). *P < 0.05 when compared with "before SA" value. SA = spinal anesthesia; CBFV = cerebral blood flow velocity.
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Discussion
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This study demonstrates that, in FPI, spinal anesthesia with bupivacaine induces a significant decrease in diastolic CBFV and a significant increase in RI associated with a decrease in mean ABP.
We used TCD to measure CBFV of the MCA. The reliability of this technique has already been documented in children (11). We used RI to reduce the error induced by variations of the angle between ultrasound emitted beam and the vessel and we controlled the Doppler position by echographic two-dimensional imaging to have more reproductive measurements. RI is a well-accepted tool and is largely used to evaluate cerebrovascular resistances.
CBFV may vary according to body temperature, hematocrit, and PaCO2 (10,12). In the current study, we maintained normothermia by controlling the operative room temperature and by covering the patients with a warming blanket. The greater the blood viscosity increase, the greater was the CBFV decrease. In this study, surgery did not induce bleeding, and the amount of IV infusion was minimal, making unlikely any significant change in hematocrit. Finally, spinal anesthesia does not induce any change in PaCO2. Patients were free from any hypoxemic pulmonary disease. We thus considered that change in PaCO2 were also unlikely during spinal anesthesia in the FPI breathing spontaneously in air.
In our study, spinal anesthesia caused a significant decrease in systolic, diastolic, and mean ABP within 5 minutes that was confirmed at 10 minutes. Dohi et al. (5) have demonstrated that spinal anesthesia produces less hypotension in infants and children than in adults. In their study, little or no decrease in systolic ABP occurred in children younger than 5 years of age, whereas systolic ABP decreased significantly after spinal anesthesia in adults. According to these authors, a less well developed sympathetic nervous system and a smaller lower extremity blood volume compared with adults might explain these results. In addition, Oberlander et al. (13) demonstrated that hemodynamic stability was the consequence of a decrease in parasympathetic cardiac modulation in FPI. In these 2 previous studies, spinal anesthesia was performed with 1 mg/kg of 0.5% hyperbaric tetracaine with dextrose plus epinephrine. Conversely, Mahé and Ecoffey (14) have shown that spinal anesthesia with 1.25 to 5 mg isobaric 0.5% bupivacaine + epinephrine produces a significant decrease in systolic and diastolic ABP. These results are in agreement with our data. Spinal anesthesia with bupivacaine and tetracaine have been previously compared (15). The result of this study showed comparable changes in ABP after spinal anesthesia that were independent of the local anesthetic solution. It is noteworthy that the isobaric 0.5% bupivacaine dose given in the current study (1 mg/kg) is larger that commonly used by several authors. Nevertheless it is in agreement with French experts’ recommendations1 and with other authors (16,17). Larger doses of bupivacaine are required in infants compared with adults; this may be related to the larger volume of distribution and to the relative increased surface area of the spinal cord and nerve roots (16,18). The large dose we used might explain the decrease in ABP that we noticed and the results of our investigation may not be applicable to patients given smaller doses.
We observed that spinal anesthesia leads to a significant decrease in diastolic CBFV and a significant increase in RI. Newell et al. (19) have previously demonstrated a correlation between CBFV changes and CBF. TCD allows evaluating cerebral vascular resistances using the RI (9). We conclude that CBFV and RI changes relate to CBF and cerebral vascular resistances changes, respectively. Thus, spinal anesthesia induced ABP changes lead to a significant decrease in CBF in FPI and a significant increase in cerebral vascular resistances.
In FPI, the normal and pathological CBFV values are still unknown. The CBFV changes measured contemporary to ABP changes in this study suggest that cerebral autoregulation is impaired in healthy FPI. Lou et al. (20) were the first authors to describe an impaired autoregulation in neurologically healthy preterm infants, using 133Xe clearance to measure cerebral autoregulation. This was supported later by Panerai et al. (7,21) using dynamic measurements. They have demonstrated that CBF autoregulation was absent in FPI. In these patients, changes in CBF mirror changes in ABP. These passive changes in CBF make these infants vulnerable to any hemodynamic disturbances. The decrease in CBFV we demonstrated might be important because FPI are supposed to have fragile neurological function. Whether the changes in CBFV secondary to spinal anesthesia may have long-term consequences on the neurological outcome cannot be determined.
Spinal anesthesia instead of general anesthesia has been recommended in FPI to reduce the incidence of postoperative apnea. The results of the current study challenge this well-accepted recommendation. The evidence of a decrease in CBFV related to change in ABP is at least a plea for rapid treatment of hypotension by the administration of vasoconstrictive drugs in FPI or a decrease in the local anesthetic spinal dose used in FPI.
In conclusion, we have documented that spinal anesthesia entails a significant decrease in diastolic CBFV with an increase in RI in FPI scheduled for inguinal hernia repair. This would be explained by a decrease in ABP secondary to spinal anesthesia and impaired cerebral autoregulation. Further studies are needed in FPI to evaluate the consequences on neurological outcome of these transient changes in CBFV.
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Footnotes
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1 Conference d’experts: anesthésie locorégionale chez l’enfant. Ann Fr Anesth Reanim 1997;16:2–7. 
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Accepted for publication November 6, 2003.
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Abstract
Introduction
