Anesth Analg 2001;93:166-170
© 2001 International Anesthesia Research Society
NEUROSURGICAL ANESTHESIA
Sodium Nitroprusside Compared with Isoflurane-Induced Hypotension: The Effects on Brain Oxygenation and Arteriovenous Shunting
William E. Hoffman, PhD,
Guy Edelman, MD,
Rick Ripper, CVT, and
Heidi M. Koenig, MD
Department of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois
Address correspondence and reprint requests to William E. Hoffman, PhD, Department of Anesthesiology, M/C 515, University of Illinois at Chicago, 1740 W. Taylor St., Chicago, IL 60612. Address e-mail to whoffman{at}uic.edu
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Abstract
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We compared sodium nitroprusside (SNP)-induced hypotension with 3% isoflurane-induced hypotension with regard to brain tissue oxygen pressure (PtO2), middle cerebral artery (MCA) blood flow, and cerebral arteriovenous shunting. Eight dogs were anesthetized with 1.5% isoflurane. After a craniotomy, a probe was inserted into the left frontoparietal brain cortex to mea-sure tissue gases and pH. Blood flow was measured in a secondary branch of the MCA by a flowprobe. Mea-surements were made during baseline 1.5% isoflurane, during 1.5% isoflurane and SNP-induced hypotension or 3% isoflurane-induced hypotension to a mean pressure of 60–65 mm Hg, and during continued treatment with SNP or 3% isoflurane with blood pressure support to baseline levels with phenylephrine. Shunting was calculated from arterial, sagittal sinus, and tissue (indicating capillary) oxygen content. During hypotension with SNP, PtO2 decreased 50%, and shunting increased 50%. During hypotension with 3% isoflurane, PtO2 and shunting did not change. Blood pressure support increased PtO2 and MCA flow during both SNP and 3% isoflurane treatment. These results show that SNP is a cerebrovasodilator but that hypotension will decrease PtO2, probably because of an increase in arteriovenous shunting and a decrease in capillary perfusion.
Implications: We measured brain arteriovenous shunting and tissue oxygen pressure(PtO2)during a 40% decrease in blood pressure induced by sodium nitroprusside (SNP)or 3% isoflurane. Large-dose isoflurane maintainedPtO2 withno change in shunting. SNP infusion decreasedPtO2 50%and increased shunting 50%. This suggests that SNP-induced hypotensiondecreasesPtO2because of a decrease in capillaryperfusion.
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Introduction
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We previously reported that 3% isoflurane administration in dogs will maintain brain tissue oxygen pressure (PtO2) at baseline levels even though arterial blood pressure decreases 40% (1). When blood pressure is supported with phenylephrine, 3% isoflurane increases PtO2 compared with 1.5% isoflurane. This shows that the cerebrovasodilator effect of large-dose isoflurane can maintain brain tissue oxygenation, even though it produces hypotension and abolishes cerebral autoregulation (2). We have questioned whether this effect is the same for other cerebrovasodilators, such as sodium nitroprusside (SNP), or whether SNP may decrease PtO2 because of arteriovenous shunting (3–5). However, SNP decreased infarct size after transient focal cerebral isch-emia in rats, and this effect may be caused by its action as a nitric oxide donor and cerebrovasodilator (6). We compared SNP and 1.5% isoflurane-induced hypotension with 3% isoflurane-induced hypotension for the effect on PtO2, middle cerebral artery (MCA) blood flow, and cerebral arteriovenous shunting.
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Methods
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This study was approved by the Institutional Animal Care Committee, and experiments were performed at the West Side Veterans Administration Animal Research Facilities in Chicago. Eight nonpurposely bred male hounds were used in this study. Dogs were fasted overnight. On the day of the study, the dog was anesthetized with 5 mg/kg propofol and intubated and ventilated with 1.5% isoflurane and an inspired oxygen concentration of 30%. Catheters were inserted into the femoral artery for blood pressure recording and blood gas sampling and into the femoral vein for fluid and drug administration. Sterile saline was infused IV (4 mL · kg-1 · h-1) for fluid maintenance. A 4-cm-diameter craniotomy was performed over the left frontoparietal region and the dura incised and retracted.
A Neurotrend probe (Codman, Newark, NJ) was calibrated on the day of the study by using precision gases. The probe is 0.5 mm in diameter, and four sensors measuring pH, carbon dioxide pressure (PCO2), temperature, and oxygen pressure are contained in the final 2 cm. The probe was inserted 2 cm into the cortex, parallel to the surface of the brain. A secondary branch of the MCA feeding the region of probe insertion was isolated. A 1.5-mm Transonics (Transonics Inc., Ithaca, NY) flowprobe was placed on this branch of the MCA, and conducting gel was applied to produce an adequate blood flow signal. The sagittal sinus was catheterized with PE50 tubing. When cerebral surgery was complete, the craniotomy site was packed with sterile gauze soaked with saline to exclude extraneous light. The end-tidal isoflurane concentration was decreased to 1.5% ± 0.1%, and the dog was allowed to stabilize for 45 min. Arterial PCO2 was adjusted to 36 ± 2 mm Hg, and inspired oxygen concentration was maintained at 30%, with the balance nitrogen. Brain temperature was maintained at 37°C with a warming blanket.
After the 45-min equilibration period, arterial and sagittal sinus blood gas samples were obtained, and MCA flow, brain tissue gases, and pH were measured as baseline. Hypotension was then induced by IV infusion of SNP (20–100 µg/min) or by increasing end-tidal isoflurane to 3.0% ± 0.2%. The target mean arterial blood pressure (MAP) for both hypotensive treatments was 60 to 65 mm Hg. After a 5-min equilibration at the hypotensive level, a second measure was made of arterial, venous, and tissue gases and pH. SNP infusion or 3% isoflurane was maintained at constant levels, and blood pressure was supported to baseline levels with IV phenylephrine infusion (0.5–2.0 µg/min) for the third measure. The choice of the hypotensive treatment with SNP or 3% isoflurane was made in random order, with 1 h of equilibration before the start of the second hypotensive treatment.
Arterial and sagittal sinus blood gases and pH were measured with an Instrumentation Laboratories 1202 Blood Gas Analyzer (Minneapolis, MN). At the end of the study, the dog was killed with a euthanasia solution.
Physiologic shunt fraction was calculated in brain from oxygen content in the artery, sagittal sinus, and capillary by using the Neurotrend tissue value to estimate capillary gases (7). Oxygen content was calculated from oxygen pressure in each case and corrected for pH and temperature by using the oxygen dissociation curve for the dog (8,9). For the capillary mea-sure, pH was estimated from tissue PCO2, assuming the normal CO2/pH relationship for each dog’s blood. Shunt fraction was calculated as follows:
equation
Data are reported as mean ± SD. Physiologic variables were compared between baseline, hypotensive treatment, and blood pressure support with phenylephrine within each group by using a repeated mea-sures analysis of variance with Tukey’s tests for post hoc comparisons. Comparisons between groups were made by analysis of variance with Tukey’s tests for post hoc comparison. A P value <0.05 was considered significant.
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Results
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Changes in MAP, heart rate, arterial gases, and pH are shown in Table 1. MAP was decreased to similar levels with SNP and 3% isoflurane. Phenylephrine infusion returned blood pressure to baseline levels, even though the SNP or 3% isoflurane treatments were continued. Arterial blood gases and pH were similar between the groups and did not change with hypotensive treatment.
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Table 1. Mean Arterial Pressure (MAP), Heart Rate (HR), Arterial Oxygen Tension (Pao2), Carbon Dioxide Tension (Paco2), pH, and Brain Temperature During Baseline Treatment with 1.5% Isoflurane, Sodium Nitroprusside (SNP), and 3% End-Tidal Isoflurane (Iso) Treatment and MAP Support with Phenylephrine (PE) in Eight Dogs Tested with Both Treatments
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Sagittal sinus and brain tissue gases and pH are shown in Table 2. Venous oxygen partial pressure did not change during hypotension with either SNP or 3% isoflurane, and it increased above baseline levels during blood pressure support with phenylephrine. These changes were not different between the two groups. PtO2 decreased during SNP-induced hypotension and returned to baseline levels during blood pressure support with phenylephrine. In contrast, PtO2 did not decrease during 3% isoflurane treatment and increased above baseline levels during blood pressure support. Tissue pH decreased during SNP-induced hypotension and was significantly different from 3% isoflurane.
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Table 2. Sagittal Sinus Oxygen Pressure (Pvo2), Carbon Dioxide Pressure (Pvco2), pH (pHv), and Brain Tissue Oxygen Pressure (Pto2), and Carbon Dioxide Pressure (Ptco2) and pH (pHt), with 1.5% and 3% Isoflurane (Iso) During Phenylephrine (PE) Induced Increases in Mean Arterial Pressure (MAP) in Eight Dogs
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MCA blood flow and arteriovenous shunting are shown in Figure 1. MCA blood flow increased 20% during SNP treatment alone and 190% when blood pressure was supported with phenylephrine (both P < 0.05). MCA flow was unchanged during 3% isoflurane alone and increased 25% during 3% isoflurane with blood pressure support (P < 0.05). Arteriovenous shunting increased from 27% to 54% during SNP treatment and blood pressure support (P < 0.05). In contrast, shunting did not change during 3% isoflurane treatment.
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Figure 1. Arteriovenous shunt (top) and middle cerebral artery (MCA) blood flow during isoflurane and sodium nitroprusside (SNP) infusion. Data reported as mean ± SD. Asterisks indicate difference from baseline treatment with 1.5% isoflurane. BP = blood pressure.
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Discussion
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These results show that during hypotension to a MAP of 62 mm Hg induced by 3% isoflurane, MCA flow and PtO2 were statistically unchanged compared with baseline. This is consistent with the cerebrovasodilator effects of large-dose isoflurane (2). Even though this concentration of isoflurane abolishes cerebral autoregulation, the ability to maintain tissue oxygenation is intact (1,2). There was no change in brain arteriovenous shunting with 3% isoflurane compared with baseline measures. Similar to 3% isoflurane, SNP produced hypotension and maintained MCA blood flow. However, PtO2 decreased 50% and arteriovenous shunting increased 50% with SNP. In addition, tissue pH decreased during the hypotensive phase with SNP. This suggests that capillary perfusion during SNP-induced hypotension was inadequate and that tissue hypoxia and acidosis resulted. An increase in shunting with SNP seems to be a primary factor producing tissue hypoxia.
SNP is a cerebrovasodilator, although the potency of this effect is not well defined. In dogs, IV SNP maintained cerebral blood flow (CBF) until MAP decreased <65 mm Hg (10). With further decreases in MAP, CBF decreased. In rats, CBF decreased more with SNP-induced hypotension to 70 mm Hg compared with nitroglycerin and large-dose enflurane (11). Although SNP may disrupt autoregulation, the cerebrovasodilator effect of the drug may be adequate to maintain CBF (9). In our study, SNP maintained MCA blood flow during hypotension and increased CBF when MAP was supported with phenylephrine. Our data suggest that SNP is a potent cerebrovasodilator that will maintain CBF during a 40% decrease in MAP.
Despite its ability to maintain MCA blood flow, SNP-induced hypotension decreased PtO2 50%. This is likely because of an increase in arteriovenous shunting and a decrease in capillary perfusion during SNP. SNP increases the intrapulmonary shunt fraction more than a comparable dose of nitroglycerin (12). Although SNP may also decrease arterial oxygenation, this is not consistent (12,13). When SNP infusion decreased MAP 20%–25%, capillary blood flow in skeletal muscle decreased 50%, and tissue oxygenation decreased 21% (4). A similar hypotensive treatment with adenosine produced no change in capillary flow or tissue oxygenation. A micropuncture study in skeletal muscle showed that when MAP was decreased from 70 to 40 mm Hg in hamsters, precapillary resistance decreased, but venule intravascular pressure increased (5). Functional capillary density decreased, and tissue hypoxia was present. These changes were not seen during hypotension with nitroglycerin. Crystal and Salem (3) reported that when SNP was infused to decrease MAP 50%, myocardial oxygen decreased, but oxygenation in the coronary sinus did not change. These studies and our results support the conclusion that SNP produces vasodilation and shunting in skeletal muscle and myocardial and brain tissue. This may decrease capillary perfusion and increase oxygen content in venous effluent. Comparable hypotensive treatments with adenosine, nitroglycerin, or isoflurane produce less arteriovenous shunting and maintain tissue oxygenation in skeletal muscle and brain, respectively.
Even though 3% isoflurane produced hypotension similar to SNP infusion, PtO2 did not decrease. Subsequently, PtO2 increased during 3% isoflurane when MAP was supported with phenylephrine. This is likely because of the cerebrovasodilatory effect of 3% isoflurane, because phenylephrine has minimal cerebrovasoconstrictor activity (14). Large concentrations of isoflurane or desflurane can increase PtO2 if blood pressure is supported (1,15). This may be related to the ability of inhaled anesthetics to produce cerebrovasodilation and enhance collateral circulation. At the same time, there was no increase in arteriovenous shunting (1). If capillary perfusion is related to tissue oxygenation, our results suggest that 3% isoflurane maintained capillary perfusion better than SNP. Endrich et al. (5) confirm that SNP increases artery to venous shunt flow rather than capillary perfusion (5). This agrees with Newberg et al. (16), who showed that SNP-induced hypotension to a MAP of 40 mm Hg in dogs decreased brain tissue adenosine triphosphate and increased tissue lactate compared with nonhypotensive controls. In contrast, isoflurane induced hypotension to the same MAP that produced no change in adenosine triphosphate or lactate compared with control. These results are consistent with the ability of large-dose isoflurane to maintain capillary perfusion, tissue oxygenation, and brain energy state better than a similar hypotensive level induced by SNP.
It was noted that during SNP infusion with phenylephrine for support of blood pressure, there was a decrease in arterial pH. This occurred without a change in arterial, sagittal sinus, or tissue PCO2. It is possible that acidosis during this treatment may have enhanced arteriovenous shunting. However, we found that metabolic acidosis produced by IV infusion of 0.1 N hydrochloric acid in dogs decreased arterial pH from 7.30 to 6.79 without a significant change in arteriovenous shunt fraction (unpublished results). This suggests that metabolic acidosis is not associated with an increase in brain arteriovenous shunting. The increase in shunting seen in this study during SNP and phenylephrine infusion is probably caused by the continued effect of SNP, because phenylephrine did not increase shunting in 3% isoflurane-treated dogs.
In summary, when SNP was infused to decrease MAP 40%, MCA blood flow, venous oxygen partial pressure, and sagittal sinus pH were maintained. However, brain arteriovenous shunting increased 50%, PtO2 decreased 50%, and tissue pH decreased with SNP. These results suggest that brain venous measures provide an incorrect indication of capillary perfusion with a drug, such as SNP, that can produce shunting. Further, our data show that SNP-induced hypotension under 1.5% isoflurane produces a greater risk of tissue hypoxia and acidosis compared with the hypotension induced by 3% isoflurane alone. We conclude that clinicians should consider limiting the use of SNP for controlled hypotension in patients susceptible to ischemia.
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References
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Accepted for publication February 14, 2001.
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Abstract
Introduction
