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down) can guide fluid therapy during pheochromocytoma surgery
down) peut guider le remplissage vasculaire pendant la résection d’un phéochromocytome]
From the Federation of Anesthesia and Intensive Care, University Hospital, Lille, France.
Address correspondence to: Pr. Benoît Tavernier, Département d’anesthésie réanimation chirurgicale 1, Hôpital Roger Salengro, CHU de Lille, 59037 Lille cedex, France. Phone: 00 320 44 40 74; Fax: 00 320 44 49 07; E-mail: btavernier{at}chru-lille.fr
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Abstract |
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down) of the respiratory systolic pressure variation in order to assess its ability to guide fluid therapy in 13 patients undergoing pheochromocytoma surgery.
Methods: The arterial pressure waveform was recorded via a 20-g radial artery catheter. down was measured during abdominal exploration (baseline), after fluid loading, before and following tumour resection, and during treatment of arterial hypotension.
Results: At baseline, down ranged between 1 and 15 mmHg (median: 3 mmHg). Volume loading (500 mL colloid over 20 min) performed during abdominal exploration significantly reduced down (P = 0.001) and resulted in down values 
2 mmHg in all 13 patients. The down measured immediately before resection was larger in patients who had arterial hypotension (systolic arterial pressure (SAP) < 90 mmHg) following tumour removal than in other patients [4 (1–10) vs 1 (0–3) mmHg; P = 0.04]. During hypotension, down was greater in patients where fluid replacement restored SAP than in patients where fluids were ineffective and vasopressors needed [down: 4 (3–9) vs 1 (1–2) mmHg; P = 0.03].
Conclusion: During pheochromocytoma surgery, a down 2 mmHg appears to indicate minimal intravascular volume depletion. down measurements could be used to guide fluid therapy for the prevention and treatment of arterial hypotension following pheochromocytoma removal.
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Introduction |
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Recent studies have suggested that analysis of the arterial pressure waveform during mechanical ventilation provided reliable estimation of cardiac preload.7–11 The arterial systolic pressure variation [the difference between maximal and minimal systolic arterial pressure (SAP) values during one mechanical breath] and its delta down component (down, = apneic - minimum systolic blood pressure) have been shown to be sensitive indicators of hypovolemia.7–10 In anesthetized and mechanically ventilated subjects, a down 2 mmHg indicated the absence of hypovolemia,9 but only preoperative measurements were reported. The aim of this study was to assess the usefulness of down measurement for both interpretation and treatment of arterial hypotension following pheochromocytoma resection.
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Methods |
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Arterial pressure variation
Following induction of anesthesia, a 20-g radial artery catheter was inserted as part of the routine monitoring for pheochromocytoma surgery. The analogue output from the monitor (Monitor M1165/66A; Hewlett-Packard, Les Ullis, France) was used via an analogue-to-digital converter to record the arterial pressure onto a computer (Toshiba 300 CDS, Tokyo, Japan). Recording and analysis used a customized acquisition software (Bionet 1.2, ITM, Lille University Hospital, Lille, France). The arterial pressure curve was recorded for 20 to 30 sec. The value of the SAP during a period of five to ten seconds of end-expiratory pause was used as a reference pressure to measure down (Figure 1
). Pressure waveform analysis was performed off-line with the reviewer unaware of the clinical circumstances at the time of recording. down was determined during the two or three respiratory cycles that immediately preceded the apnea period. In preliminary experiments, the inter-observer variability in determining the magnitude of down was 1 mmHg.
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down were made in the following sequence: 1) at the beginning of intervention; 2) before and after "typical" volume loads (i.e., 500 mL colloid over 15–20 min with no brisk change in arterial pressure or heart rate strongly suggestive of acute catecholamine release, and no change in nicardipine infusion) during abdominal exploration; 3) immediately before ligation of the draining vein; 4) at the time of lowest arterial pressure following tumour resection; 5) after volume loading (500–1000 mL colloid), given when SAP < 90 mmHg following tumour resection; and 6) after bolus iv injection of ephedrine, in case of ineffectual fluid replacement (defined as the absence of restoration of SAP 
90 mmHg following volume load). SAP, heart rate, tidal volume and airway pressures were recorded simultaneously with each measure of down. Respiratory variables were obtained from the ventilator monitoring panel, and quasi-static respiratory compliance was calculated according to standard equation.
Analysis
Results are expressed as median and range. The changes in down, SAP, and heart rate induced by "typical" volume loads during abdominal exploration as well as by tumour resection were assessed using Wilcoxon’s rank sum test. The values of down measured immediately before ligation of the draining vein were analyzed according to the incidence of arterial hypotension (SAP < 90 mmHg) following tumour resection (Mann-Whitney test). Then, the down values measured following tumour resection were analyzed according to the effectiveness of subsequent volume loading (restoration of SAP 90 mmHg; Mann-Whitney test). Finally, Spearman coefficient was used to assess correlation between changes in SAP and down during tumour removal. A P value < 0.05 was considered significant.
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Results |
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Initial down and effect of volume loading
down ranged between 1 and 15 mmHg (median: 3 mmHg) at the beginning of abdominal exploration. At that time, tidal volume and quasi-static respiratory compliance were 640 mL (410–850) and 49 mL•cm H2O-1 (22–75), respectively. During abdominal exploration, 15 volume loads (500 mL of colloid) were performed in ten patients. At that time, nicardipine was infused at a rate of 1.4 µg•kg-1•min-1 (0.5–5). As shown in Figure 2, fluid loading reduced down (P = 0.001), whereas no significant changes in SAP [from 102 mmHg (70–127) to 112 mmHg (74–153); P = 0.11] and heart rate [from 99 beats•min-1 (55–122) to 97 beats•min-1 (51–124); P = 0.59] were observed. In addition, repeated measurements showed that following 500 mL of additional colloid in five patients, down was 2 mmHg in all 13 patients.
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down and SAP following tumour resectiondown did not change significantly [from 2 (0–10) to 2 (1–9) mmHg; P = 0.62]. There was no correlation between the individual variations in SAP and down (rho = 0.13; P = 0.60). Arterial hypotension (SAP < 90 mmHg) occurred in five out of 11 patients who had a SAP 90 mmHg immediately before ligation of the draining vein. In these patients, the down measured before resection was larger than in patients in whom arterial hypotension did not occur [4 (1–10) vs 1 (0–3) mmHg; P = 0.04].
Two patients had a SAP < 90 mmHg just before and following ligation of the draining vein. Thus, a total of seven patients were hypotensive after tumour resection. At that time, down was greater in the four patients where volume loading (500 mL colloid) restored arterial pressure (Figure 1A
) than in the three remaining patients where SAP did not change following fluid replacement (500–1000 mL; Figure 1B) but responded to ephedrine [6–9 mg; down: 4 (3–9) vs 1 (0–2) mmHg; P = 0.03].
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Discussion |
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down measurements during pheochromocytoma surgery. The results suggest that even during continuous infusion of nicardipine or large changes in blood catecholamine concentration, fluid loading reduces down to the same values as those previously reported in anesthetized normal patients.9 During tumour removal, the stability of down and the absence of correlation between changes in SAP and down strongly suggest that reduced cardiac preload is not a major mechanism of the reduction in arterial pressure characteristics of pheochromocytoma resection. However, that down before resection was larger in patients where SAP decreased to less than 90 mmHg suggests that the occurrence of arterial hypotension is favoured by pre-existing reduced cardiac preload. Thus, down measurements before tumour resection may contribute to predict arterial hypotension after tumour removal. Finally, down measured at the time of lowest arterial pressure could be used to guide fluid therapy, in accordance with previous studies performed in other conditions.8–10
During abdominal exploration, down varied widely, but fluid expansion resulted in a down of 2 mmHg or less in all patients. These results are very similar to those obtained in anesthetized and mechanically ventilated subjects during graded hemorrhage and subsequent volume replacement.9 In that study, down was smaller after hetastarch than at baseline, and a down 2 mmHg appeared to indicate the absence of hypovolemia. Both studies thus suggest that a down 2 mmHg may constitute a reasonable end-point to ensure minimal intravascular volume depletion in anesthetized patients. Our results, however, extend the former observations to patients receiving nicardipine in various dosages, before and following pheochromocytoma resection, and suggest that large and rapid changes in systemic vascular resistance do not alter the value of down for the assessment of cardiac preload.
Our results suggest that a small down before ligation of the draining vein may reduce the risk of arterial hypotension following tumour removal. This is consistent with previous studies indicating that adequate fluid resuscitation is important for the prevention of severe hypotension at this stage of pheochromocytoma surgery.1,5,13 However, the values measured at that time in patients in whom arterial hypotension occurred after tumour removal overlapped those measured in other patients. This underlines that the predominant mechanism of severe hypotension following tumour resection appears to be a sharp decrease in arterial tone, and that severe hypotension may still occur in patients without pre-existing hypovolemia. Accordingly, the down did not change during tumour removal in this study, and the sole patient who presented a hypotensive episode with SAP < 70 mmHg had a down of 1 mmHg before and after tumour ablation.
Seven patients in this study had an episode of hypotension after tumour removal. This apparently high incidence is explained by the fact that we chose a SAP of < 90 mmHg to define hypotension. In fact, severe hypotension, as defined by a SAP < 70 mmHg, was observed in only one patient. Nevertheless, our results suggest that down measurements may adequately guide fluid resuscitation after tumour resection. Previous studies have shown that the main value of down is to predict the response of cardiac output to fluid loading, but in patients with hypovolemia, the response to fluid therapy is usually an increase in both cardiac output and arterial pressure.10 Therefore it appears reasonable to propose that, when treating arterial hypotension following pheochromocytoma resection, a large down indicates that fluid should be given, whereas a small down ( 2 mmHg) strongly suggests that fluid resuscitation is no longer necessary and may be deleterious. In this case, vasopressors and/or inotropic agents should be used.
Several limitations must be discussed. First, as in many studies concerning pheochromocytoma surgery, the number of patients included was small, and although statistically significant differences were observed, the predictive value of down measurements before and during tumour removal could not be established. Second, simultaneous measurements of other indexes, such as central venous pressure, pulmonary artery occlusion pressure, or left ventricular end diastolic area measured by transesophageal echocardiography may have allowed to study the correlation of down with these indexes of volume status or ventricular preload. However, because several recent studies have shown that these variables are not reliable indicators of fluid responsiveness,6,14 we did not systematically measure them in our patients. The clinical relevance of our results may be questioned, since patients do not systematically exhibit severe and/or prolonged hypotension following pheochromocytoma removal. However, clinical experience and the literature show that hypotensive episodes requiring rapid treatment are not unusual and inadequate treatment may be deleterious in such circumstances.1,15–17 Finally, while a specific software was used for off-line data analysis in our study, it should be noted that, in clinical practice, down can be measured with most monitors directly from the arterial pressure trace18 or, after identification of the systemic arterial pressure as a pulmonary artery pressure, by using the "wedge measurement" procedure.19
In conclusion, the present study suggests that a down 2 mmHg, which has been proposed to define the absence of hypovolemia in anesthetized patients, can also be used in the particular conditions of pheochromocytoma surgery. Maintaining down at such small values may contribute to reduce the risk of severe arterial hypotension following tumour removal. In addition, down measurements allow to guide volume resuscitation and avoid unnecessary fluids when treating arterial hypotension after tumour resection. Since invasive monitoring of arterial pressure is routinely used during pheochromocytoma surgery, our study suggests that measurement of down could be performed systematically in these patients.
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Footnotes |
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References |
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2 Roizen MF. Anesthetic implications of concurrent diseases. In: Miller RD (Ed.). Anesthesia. New York: Churchill Livingstone Inc.; 1994: 903–1014.
3 Mihm FG. Pulmonary artery pressure monitoring in patients with pheochromocytoma. Anesth Analg 1983; 62: 1129–33.
4 Pinaud M, Desjars P, Tasseau F, Cozian A. Preoperative acute volume loading in patients with pheochromocytoma. Crit Care Med 1985; 13: 460–3.[Medline]
5 Hull CJ. Phaeochromocytoma. Diagnosis, preoperative preparation and anaesthetic management. Br J Anaesth 1986; 58: 1453–68.
6 Michard F, Teboul JL. Using heart-lung interactions to assess fluid responsiveness during mechanical ventilation. Crit Care 2000; 4: 282–9.[Medline]
7 Perel A, Pizov R, Cotev S. Systolic blood pressure variation is a sensitive indicator of hypovolemia in ventilated dogs subjected to graded hemorrhage. Anesthesiology 1987; 67: 498–502.[Medline]
8 Coriat P, Vrillon M, Perel A, et al. A comparison of systolic blood pressure variations and echocardiographic estimates of end-diastolic left ventricular size in patients after aortic surgery. Anesth Analg 1994; 78: 46–53.
9 Rooke GA, Schwid HA, Shapira Y. The effect of graded hemorrhage and intravascular volume replacement on systolic pressure variation in humans during mechanical and spontaneous ventilation. Anesth Analg 1995; 80: 925–32.[Abstract]
10 Tavernier B, Makhotine O, Lebuffe G, Dupont J, Scherpereel P. Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension. Anesthesiology 1998; 89: 1313–21.[Medline]
11 Michard F, Boussat S, Chemla D, et al. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med 2000; 162: 134–8.
12 Proye C, Thevenin D, Cecat P, et al. Exclusive use of calcium channel blockers in preoperative and intraoperative control of pheochromocytomas: hemodynamics and free catecholamine assays in ten consecutive patients. Surgery 1989; 106: 1149–54.[Medline]
13 Bravo EL, Gifford RW Jr. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 1984; 311: 1298–303.[Medline]
14 Pinsky MR. Functional hemodynamic monitoring. Intensive Care Med 2002; 28: 386–8.[Medline]
15 Shupak RC. Difficult anesthetic management during pheochromocytoma surgery. J Clin Anesth 1999; 11: 247–50.[Medline]
16 Kinney MA, Warner ME, vanHeerden JA, et al. Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg 2000; 91: 1118–23.
17 Prys-Roberts C. Phaeochromocytoma–recent progress in its management. Br J Anaesth 2000; 85: 44–57.
18 Stoneham MD. Less is more...using systolic pressure variation to assess hypovolaemia (Editorial). Br J Anaesth 1999; 83: 550–1.
19 Tavernier B. Evaluation peropératoire de la volémie. In: Société Française d'Anesthésie et de Réanimation (Ed.). Conférences d'Actualisation, Paris: Editions scientifiques et médicales Elsevier SAS et SFAR; 2001: 385–98.
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  C. Runcie, B. Tavernier, H. Solus-Biguenet, M. Fleyfel, and B. Vallet Predicting fluid responsiveness in theatre Br. J. Anaesth., April 1, 2007; 98(4): 545 - 547. [Full Text] [PDF]
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