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CARDIOVASCULAR ANESTHESIA

The Influence of Deliberate Hypotension on Splanchnic Perfusion Balance with Use of Either Isoflurane or Esmolol and Nitroglycerin

D. Andel, MD^*, H. Andel, MD^*, K. Hörauf, MD PhD^*, D. Felfernig, MD^*, W. Millesi, MD, and M. Zimpfer, MD MBA

*Department of Anesthesiology and General Intensive Care, Ludwig Boltzmann Institute of Clinical Anesthesiology and Intensive Care, and Department of Oral and Maxillofacial Surgery, Vienna General Hospital, University of Vienna, Austria

Address correspondence and reprint requests to Dorothea Andel, MD, Department of Anesthesiology and General Intensive Care, 18-20 Waehringer Guertel, 1090 Vienna, Austria. Address e-mail to dorothea.andel{at}akh-wien.ac.at

	Abstract

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Various techniques to induce deliberate hypotension (DH) have different influences on splanchnic perfusion. The aim of our study was to determine whether splanchnic perfusion is clinically impaired during DH by using either isoflurane (ISO) or a combination of esmolol and nitroglycerin (E/N). We randomized 16 patients undergoing elective maxillofacial surgery to receive either ISO (0.7%–1.8%) or E (105 g · kg^-1 · min^-1) and N (1–6 mg/h) to induce DH. General anesthesia was performed in both groups by IV midazolam 0.07 mg/kg, fentanyl 0.003 mg/kg, propofol 1.5 mg/kg, and vecuronium 0.1 mg/kg followed by a propofol infusion with 6 mg · kg^-1 · h^-1. After the induction of anesthesia, a gastric tonometer (TRIP^®NGS Catheter) and a radial artery catheter were inserted. Baseline values of gastric intramucosal pH (pHi) were determined 60 min after placement of the catheter and before the induction of DH. The pHi values were calculated every 60 min until DH was discontinued. In both groups, DH was satisfactorily established. None of the pHi values calculated was less than 7.37 in the E/N or 7.41 in the ISO group. Arterial blood lactate levels did not increase in any of the patients. We conclude that neither method of producing DH compromises splanchnic tissue oxygen balance in healthy patients. Furthermore, overall organ perfusion was sufficient in both groups, because none of the patients showed an increase in blood lactate.

IMPLICATIONS: Neither the isoflurane nor the esmolol/nitroglycerin method of producing deliberate hypotension compromises splanchnic tissue oxygen balance in healthy patients. Furthermore, overall organ perfusion was sufficient in both groups, because none of the patients showed an increase in blood lactate.

	Introduction

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Deliberate hypotension (DH) with mean arterial blood pressure values of 50–60 mm Hg optimizes surgical conditions by minimizing intraoperative blood loss during maxillofacial surgery (1). However, various techniques to induce DH may have different influences on splanchnic perfusion (2). Possible consequences of diminished splanchnic perfusion include increased microbial translocation and mucosal hyperpermeability based on ischemic damage of the intestinal mucosa (3,4).

Approximately 50%–60% of patients undergoing major surgery, even without DH, may develop transient and sometimes sustained episodes of dysoxia, even when intravascular volume replacement appears to be adequate (5). Thus it is very important to know how well the splanchnic region is perfused during surgery involving DH. Because direct measurement is invasive and difficult, a usual and very effective substitute is the measurement of gastric intramucosal pH (pHi) (5,6). By means of this quantified measurement, critical reductions in perfusion are easily identified.

In the first study to measure the effects of DH on the perfusion of various organ systems, Kick et al. (2) examined the effect of an inhaled versus an IV technique in an animal model. Isoflurane (ISO) alone was compared with a combination of propofol and alfentanil, urapidil, and ISO at small end-expiratory concentrations. The authors found, without drawing clinical conclusions from the finding, that splanchnic blood flow decreased significantly in the group anesthetized with ISO, whereas it remained stable in the combination group (2).

In our facility, ISO or a combination of nitroglycerin and esmolol (E/N) is often used to induce DH during maxillofacial surgery. We decided to investigate whether DH, induced either by ISO or E/N, causes a clinically relevant impairment in splanchnic perfusion, leading to a reduction of pHi values to <7.35 (6). Furthermore, an increase of the CO₂ gap >18 mm Hg would also represent a clinically derived cutoff that reflects an inadequacy of intestinal perfusion (7). This report presents the first results from a clinically study of this issue.

	Methods

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After receiving departmental approval and written informed patient consent, we enrolled 16 patients undergoing elective maxillofacial surgery in this prospective randomized study. After the decision of the maxillofacial surgeons to initiate DH, patients were randomly assigned to receive either ISO or E/N. Demographic data and duration of procedures for each group are shown in Table 1. Table 2 lists the individual surgical procedures. Because DH is not recommended for patients with severe systemic diseases and definite functional limitations (8), only patients classified as ASA physical status I and II were included in the study. The use of any cardiovascular medication was an exclusion criterion for participation. We mea-sured gastric pHi, which is a valid measurement of splanchnic perfusion balance (6).

Ventilation was adjusted to maintain arterial CO₂ levels between 35 and 45 mm Hg. A positive end-expiratory pressure of 5 mbar was established in all patients to prevent atelectasis. The inspiratory oxygen concentration was set to 30%. During the operative procedure, 6 mL · kg^-1 · h^-1 IV crystalloid solution was administered.

Perioperative monitoring consisted of electrocardiogram, capnography, pulse oximetry, temperature, urinary output, and invasive arterial pressure. Temperature was kept within the normal range (36°C–37°C) by using a warming device (Bair Hugger^®, Augustine Medical, Eden Prairie, MN). Immediately after the induction of anesthesia, a gastric tonometer (TRIP^®NGS Catheter; Tonometrics Division, Instrumentarium Corp. Helsinki, Finland) was placed into the stomach and filled with a phosphate-bicarbonate buffer (10). In accordance with the procedure for tonometry, baseline measurement was taken 60 min after placement of the probe, and DH subsequently was induced. Systolic arterial pressure was decreased to approximately 30% below preoperative values. However, mean arterial pressure was maintained at levels >50 mm Hg. DH was stopped 30 min before the end of surgery, and any signs of developing a rebound hypertension (defined as an increase in blood pressure to 30% above baseline values) were recorded.

In the ISO group, the dose required to induce DH ranged from 0.7 to 1.8 vol% expired ISO. In the E/N group, DH was induced with esmolol 10 µg · kg^-1 · min^-1, followed 5 min thereafter by nitroglycerin in doses ranging from 1 to 6 mg/h, until arterial blood pressure was decreased to the desired range.

The measurements of gastric PCO₂ and arterial HCO₃^- were performed (AVL 995-Hb; AVL medical instruments AG, Schaffhausen, Switzerland) to calculate gastric pHi and were taken in 60-min intervals until the discontinuation of DH. The pHi at 37°C was calculated for the appropriate equilibration period according to the following version of the Henderson-Hasselbach equation:

equation

where 6.1 is the pK for the HCO₃^-/CO₂ system in the plasma at 37°C; [HCO₃^-] is the actual bicarbonate concentration of the arterial blood sample; and PCO_2(SS) is the steady-state adjusted PCO₂ of the tonometer sample—the correction factor for an equilibration time of 60 min by using this catheter is 1.13; 0.03 is the solubility of CO₂ in plasma at 37°C. Furthermore, the CO₂ -gap (i.e., the difference between arterial and gastric PCO₂) was registered. Blood lactate levels were measured at the initiation of DH and immediately after its discontinuation.

Before starting the experiments, a statistical forecast of the study was performed (nQuery for Windows, Statistical Solutions, Boston, MA). On the basis of data from the literature, the intention was to detect a pHi difference between the groups of 0.1. Considering analysis with the nonparametric Wilcoxon’s ranked sum test, the calculated effect size of 1.66 (by using a common SD of 0.06) resulted in a p₁ (P(X<Y) value of 0.881. To reach a minimum power of 80% (ß = 0.2) and an error of 5%, a study population of 16 patients was necessary. For statistical evaluation, demographic data and pHi values for the two groups were compared by using the Wilcoxon test. P values <0.05 were considered statistically significant.

	Results

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There were no significant differences among the patients in their demographics or the duration of their surgical procedures (Table 1). DH was satisfactory produced in both groups (Fig. 1). The gastric pHi values calculated over the course of DH are listed in Figure 2. In no patient, either in the ISO or in the E/N group, did the pHi value decrease to <7.35, the critical value in patients with normal arterial pH, during the study period. Furthermore, the CO₂ gap never exceeded 10 mm Hg. There was no statistically significant difference in the pHi values between the ISO and E/N groups. In one patient in the ISO group, high pHi values were recorded that might reflect measurement problems, although we used a phosphate-bicarbonate buffer to fill the gastric balloon to eliminate such problems. However, because of the high values, the measurement was repeated and consistently showed the same results. Therefore, we decided not to exclude this patient from the study. In all patients, urinary output was at least 1 mL · kg^-1 · h^-1. None of the patients developed intraoperative acidosis, and blood lactate levels did not increase in either group during the entire DH period. None of the patients in either group experienced rebound hypertension. All patients were able to be extubated immediately after the end of the surgical procedure.

View larger version (44K): [in this window] [in a new window]   Figure 1. Hemodynamic data presented as mean ± SD. A = preinduction values; B = postinduction values; 15 to 300 = minutes after induction of deliberate hypotension; C = posthypotension values.

View larger version (46K): [in this window] [in a new window]   Figure 2. Gastric intramucosal pH values. Patients (P) are represented by their case number, overlaid by the median values and interquartile range at the time points.

	Discussion

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Although the beneficial effects have been controversially discussed in the literature (11), DH is most often used to reduce blood loss and operation time during maxillofacial surgery (12). The use of DH entails risks, because long operation periods in maxillofacial surgery often mean maintaining a low arterial blood pressure for several hours. As a result, splanchnic perfusion might be decreased to critical values for extended periods. Furthermore, the effects of hypotension on various organ beds are varied, complex, and not easy predictable. For example, autoregulation in the intestine is less pronounced than in the kidney, and the circulatory control of splanchnic perfusion depends not only on cardiac output but also on ₁-mediated vasoconstriction, caused in part by neuroendocrine responses to surgery and anesthesia (13). Additionally, different techniques to induce DH have different effects on splanchnic perfusion (14,15).

Research on these issues has resulted in only a few preclinical studies that provide data on splanchnic perfusion during systemic hypotension. Furthermore, despite the evidence that different methods of inducing DH lead to varying diminution in splanchnic blood flow, there are no data on whether, or how much, these methods influence homeostasis of the splanchnic region.

An important investigation in the examination of splanchnic perfusion during DH is the study of Kick et al. (2). In this study, renal blood flow decreased equally in the two groups, whereas splanchnic blood flow decreased by 36% in the ISO group but maintained stable in the Urapidil group. The decrease in mean arterial pressure in the ISO group, in contrast to the Urapidil group, was mainly an effect of reduced cardiac output. The authors concluded that the clinical effect of these findings needed to be evaluated in further investigations.

We used pHi values as an indirect assessment in this study. The pHi has been proved to be a useful variable for monitoring the clinical effect of diminished gut perfusion on homeostasis of the splanchnic region (16). Assuming normal blood pH values, if pHi does not decrease <7.35, a reduction in splanchnic perfusion is without clinical relevance (17). Furthermore, the measurement of the CO₂ gap between intragastric and arterial CO₂ is an even better variable for oxygen imbalances in the gut (18,19).

However, measurement of the pHi or CO₂ gap is not validated for differentiating changes in splanchnic perfusion as long as the oxygen balance is maintained. Therefore, our data are limited with respect to finding differences between the two groups, although we can exclude a clinically relevant impairment of splanchnic oxygen balance. Further limitations of our study include the issue that DH in some patients was shorter than 300 min, and hence numerous data points were missing at the later time points.

Unlike Kick et al. (2), we used ISO in combination with fentanyl and propofol. Thus, the ISO dosage needed to induce DH was considerably smaller (0.7%–1.8%) than in the study of Kick et al. (2) (3.12% ± 0.1%). The finding that all measured pHi values in our study remained >7.41 in the ISO group is possibly caused by the smaller amount of ISO administered and the additional analgesic effect of fentanyl in decreasing surgical stress. In our IV group, we used a combination of E/N rather than urapidil (which has an half-life of approximately 1.8 hours) to avoid drug accumulation. Although we cannot exclude the possibility that splanchnic perfusion was diminished in the ISO or the E/N group, homeostasis of splanchnic perfusion remained undisturbed in both groups because no decrease of the gastric pHi below critical values or increase of the CO₂ gap >10 mm Hg was observed.

During the study period there was no significant difference between the two groups in the measured pHi values. None of the patients in either group developed an intraoperative acidosis or had an increase of blood lactate levels above normal values.

We conclude—with the limitation of the relatively small number of patients and the indirect nature of the single assessment of splanchnic perfusion—that the use of ISO up to 1.8 vol%, as well as a combination of esmolol (10 µg · kg^-1 · h^-1) and nitroglycerin (1–6 mg/h) with fentanyl for inducing DH are both safe techniques with respect to splanchnic perfusion balance in ASA I and ASA II patients.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Andel, D. Articles by Zimpfer, M. Search for Related Content PubMed PubMed Citation Articles by Andel, D. Articles by Zimpfer, M. Related Collections Cardiovascular