Acta Anaesthesiol Scand 2002; 46: 561–566 Copyright C Acta Anaesthesiol Scand 2002Printed in Denmark. All rights reserved

ACTA ANAESTHESIOLOGICA SCANDINAVICA

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Monitoring arterial blood pressure during whole bodyhyperthermia

T. KERNER1, M. DEJA1, O. AHLERS1, B. HILDEBRANDT2, A. DIEING2, H. RIESS2, P. WUST3 and H. GERLACH1

1Department of Anesthesiology and Critical Care Medicine, 2Department of Hematology and Oncology, 3Department of Radiology, Charite MedicalCenter, Virchow Hospital, Humboldt University, Berlin

Background: For monitoring of arterial blood pressure (ABP)during whole body hyperthermia (WBH) different methodshave been recommended. This investigation was performed toevaluate the agreement of invasive measurements at varioussites, and to compare invasive and non-invasive methods ofABP monitoring under conditions of a heat-induced extremevasodilation.Methods: In 19 patients, 48 treatments with WBH were per-formed. Measurements of ABP in the radial and femoral arteryby oscillometry and by sphygmomanometry were taken at fourtemperature levels during WBH (37, 40, 41.8 and 39æC).Results: Significant differences were observed between invasiveand non-invasive methods for systolic ABP, with higher valuesfor non-invasive measurements. When compared with both in-vasive measurements for diastolic blood pressures, sphygmom-anometry gave higher values and oscillometry gave lower

RESULTS of recent studies suggest that whole bodyhyperthermia (WBH) may play an important role

in treating some tumor entities by improving the ef-fect of cytostatic treatment, especially in patients withcancers that are refractory to conventional chemo-therapy (1–3). A special WBH method known as sys-temic cancer multistep therapy (sCMT) consists of atreatment that uses cytostatic drugs during systemicheating of the body to 41.8–42.2æC, hyperoxemia andhyperglycemia (4, 5). Besides the careful selection ofpatients, appropriate anesthesiologic monitoring is apivotal prerequisite in ensuring the feasibility andsafety of WBH/sCMT (6).

During recent years an increasing number of WBHtreatments in patients with various malignant dis-eases has been observed and investigated in severalongoing multicenter studies in Europe. Previously,treatment with WBH has been repeatedly associatedwith severe toxicities, such as heart failure, pulmon-ary aspiration, hepato- and nephro-toxicity (1, 2, 7).Furthermore, the application of WBH results in exten-sive changes in hemodynamics, as described in pre-vious studies (6, 8–10). Therefore the control of ar-

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values. Sphygmomanometry also showed higher values formean ABP compared with all other techniques, while measure-ments in radial and femoral artery and by oscillometry onlydiffered by approximately 5mmHg.Conclusion: The mean arterial pressure and not the systolicand/or diastolic pressure should guide hemodynamic manage-ment during WBH. The sphygmomanometric technique is notrecommended for use during hyperthermia.

Received 16 August, accepted for publication 31 December 2001

Key words: hemodynamic monitoring; arterial blood pressure;whole body hyperthermia.

c Acta Anaesthesiologica Scandinavica 46 (2002)

terial blood pressure (ABP) under these hypercircul-atory conditions is difficult and often requires theapplication of large amounts of fluid replacement andof catecholamines.

Both invasive and non-invasive methods have beenrecommended for monitoring ABP during inducedhyperthermia (1, 2, 6, 9, 11, 12). Several studies in vari-ous clinical settings, however, have revealed remark-able differences in ABP between different sites of in-vasive measurements, and between invasive and non-invasive methods (13–22).

This investigation was performed to evaluate theagreement of invasive measurements at various sites,and of invasive and non-invasive methods for moni-toring ABP under conditions of a hyperthermia-in-duced extreme vasodilation.

Methods

Patients and performance of whole bodyhyperthermia/ systemic cancer multistep therapyIn the course of a phase I/II study of sCMT, 48 treat-ments with sCMT in 19 patients with non-resectable

T. Kerner et al.

metastatic cancers (7 women, 12 men, aged 24–64years, mean 51∫3 years, height 158–191 cm, mean173∫2 cm, weight 50–117 kg, mean 78∫4 kg) were per-formed. Informed consent was obtained from all pa-tients and the Institution’s Ethics Committee ap-proved the study. Eight patients were suffering frommetastatic colorectal cancer; five had gonadal tumors;two had ovarian cancer; and the remaining four hadsoft tissue sarcoma, cancer of the uterine cervix, can-cer of the salivary gland, and refractory malignantlymphoma, respectively. The anesthesiologic evalu-ation of all patients before sCMT revealed normalfindings in resting ECG, exercise ECG, transthoracicechocardiography, lung function, thorax X-ray, cranialcomputed tomography, and laboratory data, includ-ing thyroid function parameters.

Heating of the patients was accomplished by infra-red radiation with additional water filtering (IRA-THERM 2000A, von Ardenne Institut, Germany).After a heating period of approximately 2–3 h, thecore temperatures ranged between 41.8æC and 42.1æC.This temperature was maintained for 60 min in theplateau phase. After completion of the plateau phase,the patients cooled passively. During the rise in coretemperature, cytostatic treatment was given, depend-ing on the underlying disease, by an infusion of mito-mycin C, folinic acid and 5-fluorouracil (MFF-pat-tern), ifosfamid (I), carboplatin (C) and etoposid (E)(ICE pattern), melphalan plus ICE, IC, or CE.

Anesthesiologic managementPatients were intubated, and total intravenous anes-thesia (TIVA) was provided with propofol, remifen-tanil and vecuronium. Volume-controlled ventilationwas applied using an O2/air mixture to achieve norm-ocapnia (PaCO2 36–44 mmHg) and hyperoxia (PaO2

above 250 mmHg). In order to maintain a minimummean ABP (MABP) of at least 60 mmHg (22) in thefemoral artery and a diuresis of approximately 1 mlkgª1 hª1, crystalloid (JonosterilA, Fresenius, Ger-many) and colloidal solutions (HAESA, Fresenius,Germany), as well as human albumin 5%, were in-fused. In some patients, packed red blood cells weretransfused to preserve a hemoglobin level $9 g dLª1.In addition, norepinephrine was infused during theplateau phase in all patients. Furthermore, approxi-mately 5 g kgª1 body weight glucose was supplied byinfusion until a steady blood glucose level of above400 mg dlª1 was reached. Following sCMT and afterreaching a stable respiratory and hemodynamic con-dition, the patients were extubated and transferred toan oncologic ‘intermediate care’ unit.

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MeasurementsRadial artery blood pressure was measured using an8-cm 20-G catheter (Leader Cath, Vygon, France),which was inserted into the right radial artery ap-proximately 1–2 cm proximal to the wrist. Femoral ar-tery blood pressure was measured using a 10-cm oxy-metry-thermo-dye-dilution probe (Pulsiocath PV2024,Pulsion, Germany), which was placed into the rightfemoral artery approximately 2 cm distal to the ingui-nal ligament. Both catheters were connected to identi-cal pressure transducers (RVK-Set, Abbott, Ireland)via a 170-cm rigid pressure monitoring tubing (Com-bidyn, Braun, Germany) filled with NaCl 0.9%. Thepressure signals were continuously displayed on amonitoring system (Model 88 s, Hewlett Packard, Ger-many) and calculation was performed by taking meanvalues of the monitor-derived systolic, diastolic andmean pressures. All pressure measurements wereachieved during a 10-s expiratory hold. Invasivelymeasured mean ABP was calculated using the moni-toring system, by integrating the area under the press-ure curve. Both transducers were zeroed to atmos-phere at the level assumed to be that of the rightatrium in the supine position.

For non-invasive ABP measurements, sphygmom-anometry and oscillometry (Model 88 s, Hewlett Pack-ard, Germany) were used. Sphygmomanometry wasperformed by taking the first audible sound (phase I)as the systolic value and the muffled sound (phaseIV) as the diastolic value. Both measurements wereperformed within 60 s, over the right brachial arteryusing a standard adult arm cuff (width 15 cm). Alter-nating the sequence of the non-invasive measure-ments eliminated possible systematic errors. A MABPwas determined for oscillometry by reaching thegreatest amplitude of oscillations and MABP forsphygmomanometry was calculated by the formula:MABP Ω diastolic ABP π (systolic-diastolic ABP/3).During measurements, no additional fluids weregiven and norepinephrine doses were not changed.

All blood pressure measurements were carried outwithin 1 min at four temperature levels: after induc-tion of anesthesia at 37æC; during the warming-upphase at 40æC; 30 min after reaching the plateau levelat 41.8æC; and during the cooling-down phase shortlybefore extubation at 39æC.

Statistical analysisNon-parametric tests were used for all analyses. Dif-ferences between the four methods of blood pressuremeasurement were examined at each temperaturelevel by the Friedman test. Wilcoxon’s rank sum test

Monitoring blood pressure during hyperthermia

was used for post-hoc analysis. Significance was as-sumed at P,0.05.

Results

MeasurementsThe overall time course of the systolic, diastolic andmean ABP measured in the radial and femoral arteryby oscillometry and by sphygmomanometry is shownin Figs 1–3. Friedman-analysis revealed significantdifferences between the four methods of ABP meas-urement at all temperature levels for the systolic, andmean values, as well as for the diastolic values(P,0.0001 in all cases). Results of the post-hoc analysiswere as follows:

P The systolic blood pressures revealed significantdifferences between the invasive and non-invasivemethods at all four measuring points, with the non-invasive techniques always displaying higher sys-tolic pressures (Fig. 1).

P The diastolic blood pressure values were higher forsphygmomanometry (reaching a level of signifi-cance at 37æC) and were significantly lower for os-cillometry at all temperature levels compared withboth the invasive measurements (Fig. 2). Diastolicblood pressure values in the femoral artery wereslightly higher than those in the radial artery.

P The mean arterial blood pressures showed several

Fig.1. Course of systolic arterial blood pressure (ABP) during wholebody hyperthermia, measured by four different methods. Data areshown as mean with SEM. k Sphymomarometric, S Oscillometric,g Femoral artery, P Radial artery.

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significant differences at all four temperature levels(Fig. 3): MABP values measured in the femoral ar-tery were always slightly higher than those in theradial artery. Although differences were only smallthey reached statistical significance. Mean ABP

Fig.2. Course of diastolic arterial blood pressure (ABP) during wholebody hyperthermia, measured by four different methods. Data areshown as mean with SEM. k Sphymomarometric, S Oscillometric,g Femoral artery, P Radial artery.

Fig.3. Course of mean arterial blood pressure (ABP) during wholebody hyperthermia, measured by four different methods. Data areshown as mean with SEM. k Sphymomarometric, S Oscillometric,g Femoral artery, P Radial artery.

T. Kerner et al.

measurements in the radial artery were very simi-lar to those measured by oscillometry except for41.8æC (P,0.001). Most strikingly, MABP calculatedfrom the systolic and diastolic values determinedby sphygmomanometry were always significantlyhigher than those derived from the other tech-niques. Mean ABP measurements in the radial andfemoral artery and those determined by oscillome-try, differed only by approximately 5 mmHg.

Therapeutic measuresIn order to maintain a mean ABP (A. fem.) of above60 mmHg, patients received 2800–10, 200 ml (mean5393∫2321 ml) of crystalloid solutions and 700–3200ml (mean 2182∫794 ml) of colloidal solutions persCMT session. A maximum of two packed red bloodcells per treatment were given during 29 sCMT treat-ments in order to increase hemoglobin levels above 9g dlª1. Despite the volume replacement, a MABP $60mmHg measured in the femoral artery during the pla-teau phase could only be obtained by continuous in-fusion of norepinephrine (max. 0.5 mg kgª1minª1,mean 0.09 mg kgª1minª1). Diuresis ranged between1800 and 5800 ml (mean 3120∫1211 ml) per treatment.With the above mentioned protocol, all treatmentscould be performed without clinical problems. In ad-dition, there was no need for circulatory support dur-ing the early postinterventional phase, i.e. no admin-istration of catecholamines or volume replacementwas necessary.

Discussion

This study was performed to evaluate the agreementof invasive arterial blood pressure measurements atvarious sites, and to compare invasive with non-in-vasive monitoring techniques for ABP under hyper-thermic conditions in order to derive recommenda-tions for routine clinical management. Our resultssuggest that systolic and diastolic ABP during wholebody hyperthermia determined by oscillometry orsphygmomanometry may deviate considerably fromdirectly measured intravascular arterial pressures. Onthe other hand, the mean ABP displayed only minordifferences between the direct and the oscillometricmeasurements. Therefore hemodynamic managementduring WBH should focus on the mean arterialpressure.

Hemodynamics during whole body hyperthermiashow the characteristic signs of a hyperdynamic circu-lation, i.e. an increased cardiac output and a drop in

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systemic vascular resistance, whereas varyingchanges in the systemic arterial pressure were found(6, 9, 11). Furthermore, for ABP monitoring duringwhole body hyperthermia different techniques havebeen recommended in recent decades (1, 2, 4–6, 9, 11).Under a number of special conditions, such as in pa-tients rewarming after cardiopulmonary bypass, dur-ing intense sweating, and in septicemic patients, dif-ferences between radial-to-femoral artery as well asbetween radial artery-to-oscillometric measurementshave been reported (13–16, 18, 20, 22). The obser-vation of lower radial ABP was partly attributed tothe influences of a decreased hand vascular resistanceaccompanied by hemodilution and a decreased bloodviscosity (14, 18, 23). Furthermore, thermoregulatoryvascular phenomena such as arterio-venous shuntsand active cutaneous vasodilation are likely to con-tribute to central-to-radial artery pressure differences(24–26). Following a model of the upper extremity cir-culation, a distal vasodilation and/or proximal vaso-constriction leads to an increase in the pressure gradi-ent (23, 27). This difference may increase under con-ditions of enhanced proximal resistance because ofperipheral arteriosclerotic plaques and/or catechol-amine administration (22, 28).

In previous studies the aortic and femoral meanpressures were found to best represent the so-calledsystemic pressure (16); however the mean radial ar-tery pressure was shown to not only reliably reflectthe aortic pressure in awake men but also in morethan 90% of anesthetized patients (29). In furtherstudies during thermoregulatory vasoconstriction,femoral, radial and oscillometric mean blood press-ures were similar but systolic radial artery pressuresexceeded both femoral artery and oscillometric sys-tolic pressures. On the other hand, the radial arterysystolic and mean pressures were found to be lowerthan the femoral artery pressures, and lower than theoscillometric pressures during intense sweating,under conditions of thermoregulatory- or anesthesia-induced vasodilation, or in septicemic patients (18, 22,30). Our findings, in contrast, revealed no clinicallyrelevant differences between the systolic and diastolicpressures in the radial and femoral arteries and be-tween the mean pressures measured invasively, or byoscillometry during induced hyperthermia. In case ofa suspected considerable central-to-radial pressuredifference, it is possible to reduce the effect of an in-creased hand blood flow by wrist or hand com-pression, although this was not done in our study.Any increase in the mean arterial pressure producedby the application of this maneuver indicates a greateraortic than radial pressure (14, 31).

Monitoring blood pressure during hyperthermia

Although a good correlation between oscillometricand invasive blood pressure measurements wasshown in adults (32), under conditions of enhancedhand blood flow with a central-to-radial mean press-ure difference or during propofol-N2O anesthesia, theoscillometric mean blood pressure was found to behigher than the radial or femoral artery mean press-ure, and tends to overestimate the aortic mean bloodpressure (18, 33). Our results, in contrast, indicate onlyan agreement with regard to mean ABP, whereas con-siderable differences in the systolic and diastolic ABPbetween the oscillometric and invasive measurementswere found under hyperthermic conditions.

As possible limitations of our study, it might be ar-gued that the intravascular catheters used for themeasurement of ABP in the femoral and radial arterywere not identical. We used the femoral catheter foradditional measurements of extravascular lung water.Basic data (37æC) from Figs 1 and 2 demonstrate, how-ever, that there were no significant differences in sys-tolic and diastolic ABP between the measurements inthe femoral and radial artery. Furthermore, the invas-ive and non-invasive measurements could not becompletely carried out simultaneously. We tried toeliminate possible systematic errors by alternating thesequence of the non-invasive measurements, i.e. oscil-lometry and sphygmomanometry. Finally, other fac-tors possibly influencing the measurements such asvascular conditions (e.g. arteriosclerosis) or drug ap-plication (e.g. catecholamines) have to be considered(22).

Conclusion

The mean arterial pressure instead of the systolicand/or diastolic pressure should guide hemodynamicmanagement during WBH. The sphygmomanometrictechnique is not recommended for use during hyper-thermia.

AcknowledgementSupported by Deutsche Krebshilfe, Deutsche Forschungsgeme-inschaft (SFB 273, Grako 331)

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Address:Dr Thoralf KernerKlinik für Anaesthesiologie und operative IntensivmedizinCharite – Campus Virchow-KlinikumAugustenburger Platz 113353 BerlinGermanye-mail: thoralf.kerner/charite.de