Oxygen consumption and delivery relationship in brain dead organ

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					British Journal of Anaesthesia 1996; 76: 783–789

Oxygen consumption and delivery relationship in brain-dead
organ donors


                                                             of hypovolaemia, left ventricular dysfunction, or
Summary                                                      both. Moreover, an abnormal DO2/VO2 relationship
The oxygen delivery (DO2) and consumption (VO2)              could occur in brain-dead patients, as reported
relationship in brain-dead organ donors is un-               previously in critically ill patients [9–11]. Indeed,
known. Therefore, in a prospective study, we                 several studies have supported the hypothesis of a
determined the DO2/VO2 relationship in 21 con-               decrease in oxidative metabolism in brain-dead
secutive brain-dead patients. Patients were allo-            patients [4, 12], that could be explained by a VO2
cated to one of two groups, according to plasma              supply dependency.
lactate concentration: normal (group NL, n : 11)                The aim of this study was to measure systemic DO2
or high (92.5 mmol litre91) (group HL, n : 10).              and VO2 in brain-dead patients before and after
VO2 was measured independently, using indirect               variation in DO2, to determine the DO2/VO2 re-
calorimetry, under control conditions, during low            lationship. To ensure an accurate and valid as-
DO2 challenge with PEEP administration, and high             sessment of this relationship, VO2 and DO2 were
DO2 challenge with inflation of medical antishock            measured independently. Moreover, plasma concen-
trousers and volume expansion or blood trans-                trations of lactate may indicate if metabolism is
fusion, as required. Under control conditions, there         predominantly aerobic or anaerobic, and has been
were no significant differences between groups NL            used to assess organ donors [3, 5]. Consequently, we
and HL in haemodynamic or oxygenation variables,             tested the hypothesis that the DO2/VO2 relationship
both groups having a low VO2 (mean 114                       could differ, according to plasma concentrations of
(SD 21) ml min91 m92). In group HL there was a               lactate.
different DO2/VO2 relationship pattern, with a de-
pendent VO2 only. The mean slope of the DO2/VO2              Patients and methods
relationship was significantly higher in group HL
than in group NL (0.12 (0.09) vs 0.04 (0.07), P :            The study was approved by the Ethics Committee of
0.05). We conclude that brain death was associated           Pitié-Salpêtrière Hospital and conducted according
with a low VO2, and patients in group HL exhibited           to French legislation concerning multiple organ
DO2/VO2 dependency which was not observed in                 procurement. Brain death was certified by: a neuro-
patients in group NL. (Br. J. Anaesth. 1996; 76:             logical examination demonstrating the absence of
783–789)                                                     brainstem reflexes; an apnoea test performed with
                                                             intratrachael continuous high flow (15 litre min91) of
Key words
                                                             oxygen and after 15 min of mechanical ventilation
                                                             with an FI O2 of 100 %; absence of spontaneous
Complications, brain death. Measurement techniques, calor-
imetry. Oxygen, consumption. Oxygen, delivery.               ventilation movement associated with an arterial
                                                             PCO2 greater than 8 kPa; no electrical activity
                                                             during a 20-min electroencephalographic recording;
Transplantation of organs from brain-dead donors             absence of hypothermia (35 C) and drugs known to
has become a common therapy for patients suffering           depress the central nervous system [1, 5].
from end-stage organ failure. Many physiological                All patients had a stable haemodynamic state,
disturbances are associated with brain death, and            characterized by a mean arterial pressure greater
management of the multiple organ donor is complex            than 60 mm Hg without any change in requirements
[1]. Failure to maintain cardiovascular and body             for fluids, inotropic support, or both, in the pre-
homeostasis can induce sub-optimal organ perfusion           ceding hour, and without hepatic or renal failure.
and early graft dysfunction in the recipient [2].            During the study, fluid therapy and inotropic
However, in brain-dead patients, the optimal oxygen
delivery (DO2) required to meet the metabolic
demand and provide appropriate tissue oxygenation            OLIVIER LANGERON*, MD, PIERRE COUTURE, MD, JOACHIM MATEO,
is unknown. Oxygen consumption (VO2), calculated             MD, BRUNO RIOU, MD, PHD, JEAN-LOUIS PANSARD, MD, PIERRE
using the Fick method, has been suggested as being           CORIAT, MD, Department of Anesthesiology and Critical Care,
low in brain-dead patients [3–5]. This phenomenon            Hôpital Pitié-Salpétrière, Paris VI University, Paris, France.
                                                             Accepted for publication: January 16, 1996.
could be related either to a decrease in oxygen                 *Address for correspondence: Département d’Anesthésie-
requirements similar to that observed in anaes-              Réanimation, Hôpital Pitié-Salpétrière, 47 Boulevard de
thetized patients [6–8] or to a deceased DO2 because         l’Hôpital, 75651 Paris Cedex 13, France.
784                                                                                British Journal of Anaesthesia

support were guided by haemodynamic monitoring            sensor, a carbon dioxide infrared analyser and a
with a pulmonary artery catheter, urinary output and      flowmeter. This system has been validated pre-
laboratory estimation of plasma concentrations of         viously for accuracy, sensitivity and reproducibility
electrolytes [5]. All patients were ventilated mechan-    in the measurement of VO2 [17, 18]. The mean error
ically with an FI O2 of 40 % to maintain PaO2 9 13 kPa,   in the measurement of VO2 at baseline and after
 PaCO2 at 4.5–5.3 kPa and pH at 7.35–7.45. Oeso-          increasing VO2 is 92 % (range 97 to 3 %) [19].
phageal temperature was maintained greater than           Calibration of the apparatus was performed with a
35.5 C using heated blankets and perfusion warm-          mixture of 96 % oxygen and 4 % carbon dioxide
ing.                                                      before each use.
                                                             For each patient, measurements were performed
                                                          minute-by-minute over a 20-min period in which
                                                          variation in minute-by-minute measurements of
Haemodynamic measurements were obtained via an            oxygen consumption was less than 5 %. In each
indwelling radial artery catheter and a pulmonary         patient, during each period of the study, VO2 was
artery catheter (SP5507 S, Viggo-Spectramed, Mon-         determined as the mean of 20 measurements over a
tigny le Bretonneux, France) connected to a haemo-        20-min period. All patients were ventilated mech-
dynamic monitor (HP 78354, Hewlett-Packard,               anically with a constant FIO2 of 40 % throughout the
Andover, MA, USA). The following haemodynamic             study. Oxygen extraction was calculated by dividing
variables were measured: heart rate (HR), mean            VO2 by DO2:
arterial pressure (MAP), mean pulmonary arterial
                                                                                        !          −
                                                                   Oxygen extraction = V O 2 × D O 2 1.
pressure (MPAP) and pulmonary capillary wedge
pressure (PCWP). Cardiac output was measured in
triplicate using the thermodilution method, and the       EXPERIMENTAL DESIGN
mean was calculated. Systemic vascular resistance
                                                          The trachea was not suctioned and patients were not
(SVR) and cardiac index (CI) were calculated
                                                          turned within the 30 min before acquisition of
according to standard formulae. Transoesophageal
                                                          measurements and throughout the study. We per-
echocardiography (HP Sonos 1500, Hewlett-
                                                          formed a DO2 challenge to obtain changes in DO2 of
Packard, Andover, MA, USA) was performed by a
                                                          at least <20 % from control DO2.
trained echocardiographer and left ventricular ejec-
                                                             To decrease DO2, positive end-expiratory pressure
tion fraction area (LVEFa) was calculated.
                                                          (PEEP) was administered to decrease cardiac output.
   Plasma concentrations of lactate (normal values
                                                          PEEP titration was performed to maintain MAP
-2.5 mmol litre91) were measured in control con-
                                                          greater than 40 mm Hg. The level of PEEP was
ditions using an enzymatic method (Dimension
                                                          increased up to 10 or 15 cm H2O (mean 12
apparatus, Dupont de Nemours, Wilmington, DL,
                                                          (SD 4) cm H2O). After a 15-min stabilization period,
USA). As an increase in plasma concentrations of
                                                          VO2 was measured.
lactate is thought to reflect a shift from oxidative to
                                                             To increase DO2, inflation of medical antishock
anaerobic metabolism with tissue hypoxia, brain-
                                                          trousers (MAST, Jobst Ltd, OH, USA) was under-
dead patients were divided into two groups based on
                                                          taken to increase venous return and thus cardiac
whether they had a normal (NL) or high (HL)
                                                          output [20]. The inflation pressure was approxi-
plasma lactate concentration, above 2.5 mmol litre91,
                                                          mately 40 cm H2O in the leg compartments and
in control conditions. This value was not known
                                                          30 cm H2O in the abdominal compartment. These
during the study, so that physicians performed the
                                                          levels of inflation pressure induce venous compres-
DO2 challenge blinded.
                                                          sion without arterial compression, enabling an
   Arterial and mixed venous blood was obtained to
                                                          increase in DO2 [20]. MAST inflation was followed
measure pH, partial pressures of oxygen (PO2) and
                                                          by volume expansion of 500 ml of gelation solution
carbon dioxide (PCO2), oxygen saturation (SO2) (BG
                                                          (Plasmion, Laboratories Roger Bellon, France) or
Electrolytes Apparatus, Instrumentation Labora-
                                                          transfusion of packed red blood cells if packed cell
tory, Milano, Italy) and haemoglobulin (Hb) con-
                                                          volume was less than 30 %. This DO2 challenge was
centration (Cobas Argo, Apparatus, Roche, Basle,
                                                          monitored using a pulmonary artery catheter to
Switzerland). DO2 was calculated using the following
                                                          avoid PCWP values greater than 20 mm Hg. After a
                                                          15-min stabilization period, VO2 was measured.
DO = CI ((1.34 × Hb × Sa O ) + (0.003 × Pa O )) × 10
   2                        2                 2
                                                             At the end of each 20-min period, haemodynamic
                                                          and metabolic variables were recorded, and arterial
VO2 and DO2 were measured independently to                and mixed venous blood was obtained for blood-gas
obtain reliable results, avoiding mathematical coup-      analysis. We determined VO2 in the same order:
ling of shared variables [13–16]. As reported pre-        control conditions, low DO2 and high DO2, with a
viously [17–19], VO2 was measured using a portable        recovery period between low and high DO2 charac-
indirect calorimetry system (Deltatrac, Metabolic         terized by a stable haemodynamic and metabolic
Monitor, Datax Instrumentation Corp, Helsinki,            state, as in control conditions.
Finland). This metabolic monitor measures carbon
dioxide and oxygen concentrations in inspired and
                                                          STATISTICAL ANALYSIS
expired gases per minute and calculates carbon
dioxide production and oxygen consumption during          Data are expressed as mean (SD or range). Com-
that minute. These measurements were performed            parison of control values between the two groups
on the ventilator circuit with a paramagnetic oxygen      (NL and HL) was performed using the Student’s t
DO2/VO2 relationship in brain death                                                                                       785

test and the Fisher’s exact method. Comparison of                      two groups in age, cause of brain death, mean time
several means was performed using repeated-                            lapse between causal event and brain death, body
measure analysis of variance and Newman–Keuls                          temperature, haemoglobin concentration, LVEFa
test. The relationship between VO2 and DO2 was                         and the number of patients receiving dopamine
fitted to a two-regression line model. The two best-                   throughout the study or dose of dopamine (table 1).
fit regression lines were determined by the sum of                     Under control conditions, there were no significant
least squares technique [21]. The critical DO2                         differences in haemodynamic variables between
represented the threshold, below which VO2 started                     groups NL and HL, except for cardiac index (table
to decrease with a further reduction in DO2. All P                     2). There were no significant differences between
values were two-tailed and P : 0.05 was considered                     groups for DO2 (group NL, 428 (131); range
significant. Statistical analysis was performed on a                   276–684 ml min91 m92 vs group HL, 450 (203);
computer using PCSM software (V3.1, Deltasoft,                         190–733 ml min91 m92), S v O2 oxygen extraction, ar-
Meylan, France).                                                       terial oxygen content and the arteriovenous differ-
                                                                       ence in oxygen content in control conditions (table 3).
                                                                       Moreover, a low VO2 was observed in the two groups
                                                                       (114 (21) ml min92 m92) and VO2 was not significantly
We studied 21 brain-dead patients (15 men), mean                       different between groups in control conditions (table
age 38 (range 16–53) yr. Eleven patients had a normal                  3).
(group    NL)     plasma     lactate    concentration                     During the DO2 challenge, we observed a sig-
(1.9 (SD 0.4); range 1.25–2.5 mmol litre91), and 10                    nificant increase in DO2 in both groups during MAST
patients had an elevated (group HL) plasma lactate                     application (group NL, ;24 (17) %, P : 0.05;
concentration (4.0 (0.9); 2.6–5.5 mmol litre91).                       group HL, ;48 (25) %, P : 0.05), and a significant
There were no significant differences between the                      decrease in DO2 in both groups during PEEP

          Table 1 Patient characteristics (number of patients or mean (SD or range)). BD : Brain death, LVEFa : left
          ventricular ejection fraction area. No significant differences between groups

                                                                           Group NL        Group HL
                                                                           (n : 11)        (n : 10)

                         Age (yr)                                           39 (21–53)         32 (16–51)
                         Sex (M/F)                                           8/3                7/3
                         Causes of BD
                           Head injury                                       6                  6
                           Cerebral vascular disease                         3                  2
                           Cerebral anoxia related to cardiac arrest         2                  2
                         Time lapse between causal event and BD (h)         41 (45)            35 (42)
                           No. of patients                                   8              10
                           Dose ( g kg91 min91)                              4.9 (3.5)       5.0 (2.5)
                         LVEFa (%)                                          60 (15)         58 (18)
                         Haemoglobin (g dl91)                                9.4 (2.3)       9.1 (2.5)
                         PaO2 FIO2 (mm Hg)                                 341 (87)        360 (160)
                         Body temperature (°C)                              36.7 (0.9)      37.0 (0.6)

          Table 2 Haemodynamic variables in brain-dead patients with normal lactate (NL) and high lactate (HL)
          concentrations during oxygen delivery (DO2) challenge (mean (SD)). MAP : Mean arterial pressure; HR : heart
          rate; CI : cardiac index; PAP : mean pulmonary arterial pressure; PCWP : pulmonary capillary wedge
          pressure; SVR : systemic vascular resistance. *P : 0.05 compared with control condition

                                                                                                   Overall between-
                                                            Group NL            Group HL           group
                                                            (n : 11)            (n : 10)           comparison

                  MAP                     Low DO2            58 (11)*            53 (10)*
                  (mm Hg)                 Control            83 (8)              73 (12)           ns
                                          High DO2           97 (16)*           102 (22)*
                  HR                      Low DO2           111 (25)            114 (21)
                  (beat min91)            Control           107 (29)            110 (18)           ns
                                          High DO2          106 (27)            114 (22)
                  CI                      Low DO2             2.6 (0.7)*          2.5 (1.1)*
                  (ml min91 m92)          Control             3.8 (1.1)           3.9 (1.6)        0.05
                                          High DO2            3.8 (1.0)           5.0 (1.9)*
                  PAP                     Low DO2            22 (5)*             20 (5)*
                  (mm Hg)                 Control            18 (7)              15 (5)            ns
                                          High DO2           23 (10)*            23 (5)*
                  PCWP                    Low DO2            15 (4)*             14 (4)*
                  (mm Hg)                 Control             7 (5)               6 (3)            ns
                                          High DO2           13 (7)*             13 (3)*
                  SVR                     Low DO2            18.9 (8.2)          19.8 (12.1)
                  (UI)                    Control            22.0 (7.3)          21.3 (10.7)       ns
                                          High DO2           23.6 (6.2)          21.1 (11.8)
786                                                                                                    British Journal of Anaesthesia
           Table 3 Oxygenation variables in brain-dead patients with normal lactate (NL) and high lactate (HL)
           concentrations during oxygen delivery (DO2) challenge (mean (SD)). DO2 : Oxygen delivery; VO2 : oxygen
           consumption; S vO2 = mixed venous oxygen saturation; Ca O2 : arterial oxygen content; Ca O2 − Cv O2 :
           arteriovenous oxygen content difference. *P : 0.05 compared with control condition

                                                                                                     Overall between-
                                                                Group NL         Group HL            group
                                                                (n : 11)         (n : 10)            comparison

                  DO2                       Low DO2             325 (108)*       277 (117)*
                  (ml min91 m92)            Control             428 (131)        450 (203)           ns
                                            High DO2            525 (144)*       658 (293)*
                  VO2                       Low DO2              98 (17)*        100 (13)*
                  (ml min91 m92)            Control             109 (24)         119 (16)            :0.001
                                            High DO2            104 (24)         142 (24)*
                   S vO2                    Low DO2              70 (12)*         67 (9)*
                  (%)                       Control              79 (7)           77 (10)            ns
                                            High DO2             83 (7)           79 (8)
                  Oxygen extraction ratio   Low DO2              33 (12)*         42 (18)*
                  (%)                       Control              27 (8)           33 (20)            ns
                                            High DO2             21 (6)*          26 (14)
                   CaO2                     Low DO2              12.3 (2.3)       12.0 (3.0)
                  (ml 100 ml91)             Control              12.4 (3.0)       12.0 (3.1)         ns
                                            High DO2             13.3 (1.8)       12.7 (2.5)
                   CaO2 − C VO2             Low DO2               3.5 (1.4)*       3.9 (1.1)*
                  (ml 100 ml91)             Control               2.5 (0.6)        2.7 (0.6)         ns
                                            High DO2              2.0 (0.8)        2.3 (0.7)

Figure 1 Individual relationship between oxygen consumption             Figure 2 Individual relationship between mixed venous
(VO2) and oxygen delivery (DO2) during DO2 challenge in                                       -
                                                                        oxygen saturation ( S vO2 ) and oxygen delivery (DO2) during DO2
patients with normal plasma lactate concentrations (group NL,           challenge in patients with normal plasma lactate concentrations
n : 11) (A) and high plasma lactate concentrations (group HL,           (group NL, n : 11) (A) and high plasma lactate concentrations
n : 10 (B) under three conditions: low DO2 ( ), control DO2             (group HL, n : 10 (B) under three conditions: low DO2 ( ),
( ) and high DO2 (!).                                                   control DO2 ( ) and high DO2 (!).

administration (group NL, –24 (10) %, P : 0.05;                         lationship in patients in group HL compared with
group HL, –35 (12) %, P : 0.05). In group NL,                           patients in group NL (0.12 (0.09) vs 0.04 (0.07); P :
VO2 did not increase significantly during high DO2                      0.05). This DO2/VO2 relationship, either in NL or
challenge (–4 (8) %) and was moderately decreased                       HL patients, impedes the use of a two-regression
during low DO2 challenge (–9 (9) %, P : 0.05). In                       line model in each group and consequently the
contrast, in group HL, VO2 increased significantly                      assessment of critical DO2 could not be achieved in
during high DO2 challenge (;19 (17) %, P : 0.05)                        either group (fig. 1).
and decreased significantly during low DO2 challenge                       As shown in table 3 and figure 2, we observed a
(–16 (6) %, P : 0.05) (table 3).                                                                     -
                                                                        different pattern in the S v O2 /DO2 relationship in
   There was a different pattern in the DO2/VO2                         groups NL and HL, with a significant correlation
relationship in groups NL and HL. VO2 increased                                      -
                                                                        between S v O2 and DO2 in group NL (r : 0.64, P :
with DO2 throughout DO2 challenge in patients in                        0.05), and no significant correlation in group HL
group HL, whereas patients in group NL exhibited                                                             -
                                                                        (r : 0.34). The mean slope of the S v O2 /DO2 relation-
small variations in VO2 ( VO2) during control and                       ship (fig. 2) was not significantly different between
high DO2 conditions. Nevertheless, it should be                         patients in groups NL and HL (0.07 (0.05) vs 0.05
pointed out that variations in DO2 ( DO2) were lower                    (0.05) % ml91 min m2).
in group NL compared with group HL (48 (25) %
vs 83 (26) %; P : 0.05). However, the magnitude
of VO2/ DO2 was significantly higher in group
HL than in group NL (0.13 (0.09) vs 0.05 (0.04);                        Discussion
P : 0.05).                                                              In this study, we observed a low VO2 in brain-dead
   Individual analysis of the DO2/VO2 relationship is                   patients, both in group NL and group HL (table 3),
depicted in figure 1. We observed a significant                         and a different pattern in the DO2/VO2 relationship
increase in the mean slope of the DO2/VO2 re-                           between these two groups. Pathological VO2 de-
DO2/VO2 relationship in brain death                                                                         787

pendency was noted in patients with elevated plasma      pattern compared with patients in group NL (fig. 1).
concentrations of lactate and a physiological            In group HL, the increased plasma lactate con-
DO2/VO2 relationship with a plateau was observed in      centration suggested inadequate DO2 and that tissue
patients with normal plasma lactate concentration.       oxygen requirements were no longer satisfied, and
   Brain-dead patients had low VO2 values, as            DO2/VO2 dependency was observed. Inadequate DO2
reported previously in normal humans at rest [8]         usually implies either hypoperfusion or arterial
(range of 110–150 ml min91 m92) or in critically ill     desaturation, whereas impaired oxygen utilization
surgical patients undergoing mechanical ventilation      by the tissues reflects abnormal oxygen metabolism
at rest (114 (18) ml min91 m92) or at a low level of     or dysoxia [15]. However, the lack of significant
activity (131 (21) ml min91 m92) [22]. Moreover, in      differences in haemodynamic and echocardiographic
our study, VO2 values were close to those found in       data, and blood-gas analysis between the two
anaesthetized patients, where VO2 reached a plateau      groups suggest dysoxia in group HL, with a weak
at 109 (16) ml min91 m92 or at 105 (13) ml min91 m92,    oxygen extraction and utilization by the tissues in
before and after cardiopulmonary bypass, respect-        group HL, as suggested by the non-significant
ively [6, 7]. During general anaesthesia, oxygen         difference in arteriovenous oxygen content difference
consumption decreased by 25–30 % [8, 23], cor-           between groups HL and NL. Furthermore, in group
responding to the values found in our study during       HL, the inability to obtain a critical DO2 despite a
brain death. Mechanical ventilation decreases oxy-       wide DO2 challenge with VO2 dependency would
gen consumption and minimizes oxygen uptake.             suggest a pathological DO2/VO2 dependency [24]. In
Consequently, similar VO2 values were observed           group NL, we probably did not decrease DO2 as
during brain death and general anaesthesia [23].         much as necessary to obtain critical DO2 from which
   The DO2/VO2 relationship has been studied under       VO2 begins to decrease, with a further reduction in
many circumstances [24–27], but is often a source of     DO2. Thus our results suggest that critical DO2 in
controversy, mainly because an artefactual corre-        brain-dead patients with normal plasma lactate
lation between DO2 and VO2 can occur by sharing          concentration was less than 330 ml min91 m92 which
common data for cardiac output and arterial oxygen       is the critical DO2 reported in patients during general
content leading to mathematical coupling of these        anaesthesia [6, 7]. Conversely, critical DO2 in brain-
variables [13, 16, 28]. In our study, VO2 was mea-       dead patients with elevated plasma concentrations of
sured independently in order to avoid this pitfall. We   lactate was not reached despite high DO2 levels, and
used the gas exchange method to measure VO2 with         remains unknown at present.
a metabolic monitor which had been validated                This pathological DO2/VO2 dependency has been
previously [17, 18] and exhibits a small error in VO2    reported in sepsis [10], adult respiratory distress
measurement when FIO2 is less than the critical level    syndrome (ARDS) [11], or both [9]. However, other
of 75 % [18]. In our study, FIO2 was maintained          recent studies in sepsis [13, 19, 20] and ARDS
constant at 40 %. The second criterion for a reliable    [14, 32] did not confirm this DO2/VO2 dependency,
DO2/VO2 relationship is to minimize spontaneous          probably because VO2 was measured and not calcu-
and provoked variations in metabolic demand with         lated. Thus, this is the first time that a DO2/VO2
no muscle activity to keep VO2 constant. These           dependency has been demonstrated using indepen-
conditions are achieved in brain death. Moreover,        dent measures of DO2 and VO2.
the DO2/VO2 relationship may be influenced by body          Our study indicated the occurrence of dysoxia in
temperature [29]. In our study we did not observe        some brain-dead patients, but did not enable us to
any significant difference in temperatures between       determine precisely the mechanism(s) of these
groups NL and HL which could explain the different       abnormalities. However, several hypotheses might
pattern of the DO2/VO2 relationship. Furthermore,        be suggested: (1) the event causing brain death or
we performed a DO2 challenge with PEEP adminis-          brain death itself is able to release mediators or
tration, fluid loading and MAST application, some-       induce neurohumoral dysfunction altering the micro-
times associated with blood transfusion. As reported     circulation, with oxygen diffusion impairment or
previously, VO2 is not affected by any of these          microcirculatory mismatch, such as during sepsis,
manoeuvres [16, 30]. Whereas the effects of catecho-     causing dysoxia; (2) a switch from aerobic to
lamines on cellular oxidative metabolism increase        anaerobic metabolism caused by haemodynamic
VO2 [10], dopamine is not thought to increase VO2 at     deterioration occurring during brain death may
the low doses used in our study [16, 31]. Moreover,      induce an oxygen debt in some patients and this debt
we did not observe any significant difference in         may be paid off with increasing DO2. However, our
dopamine doses between the two groups. Finally, to       study was conducted under stable haemodynamic
ascertain that a reliable DO2/VO2 relationship could     conditions, several hours after resuscitation, and
be obtained it is necessary to have at least two data    therefore this hypothesis is unlikely; (3) a reduction
pairs for each patient over a wide range of DO2          in circulating free triiodothyronine, as noted pre-
values. We collected three data pairs for each patient   viously in brain-dead patients [3, 12], may result in
over a DO2 variation of at least <20 % of control        decreased oxidative metabolism. Indeed, it has been
values, which was our minimal end-point in the DO2       shown recently that high plasma lactate concen-
challenge (table 3). As reported previously, these       trations are associated with mitochondrial impair-
different factors are essential to describe a reliable   ment in oxygen metabolism in brain-dead patients
DO2/VO2 relationship [15].                               [33].
   After DO2 challenge, we observed that patients in        Several limitations should be discussed to assess
group HL had a different DO2/VO2 relationship            the clinical relevance of our study. First, systemic
788                                                                                                  British Journal of Anaesthesia

DO2 does not assess the effectiveness of regional DO2                      MR, eds. Oxygen Transport in the Critically Ill. Chicago:
in different organs and vascular beds [26]. Local and                      Year Book Medical Publishers, 1987; 16–21.
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regional blood flow redistribution are important                           vasodilatation with prostacyclin on oxygen delivery and up-
determinants of the adequacy of both regional and                          take in critical ill patients. New England Journal of Medicine
systemic oxygen uptake, as reported previously [34].                       1987; 317: 397–403.
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may also modify the local or regional DO2/VO2                              Respiratory Disease 1986; 134: 873–878.
relationship, leading to potential organ impairment,                 11.   Danek SJ, Lynch JP, Weg JG, Dantzker DR. The de-
despite appropriate systemic DO2. Second, elevated                         pendence of oxygen uptake on oxygen delivery in the adult
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the balance between lactate production and hepatic                         aerobic to anaerobic metabolism after brain death, and
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[35] have supported the theory of obtaining supra-                         in oxygen delivery in severe adult respiratory distress
                                                                           syndrome. American Review of Respiratory Disease 1991; 143:
normal values of DO2 to prevent dysoxia and organ                          1267–1273.
system dysfunction in order to decrease mortality in                 15.   Pinsky MR. Beyond global oxygen supply–demand relations:
critically ill patients. But a recent study failed to                      in search of measures of dysoxia. Intensive Care Medicine
demonstrate any survival benefit from obtaining                            1994; 20: 1–3.
supranormal DO2 values [36]. In the management of                    16.   Hanique G, Dugernier T, Laterre PF, Dougnac A, Roeseler
                                                                           J, Reynaert MS. Significance of pathologic oxygen supply
organ donors, increasing DO2 in patients in group                          dependency in critically ill patients: comparison between
HL seems reasonable, but increasing DO2 to supra-                          measured and calculated methods. Intensive Care Medicine
normal values has yet to be demonstrated. However,                         1994; 20: 12–18.
our results do not provide evidence that increasing                  17.   Ronco JJ, Phang PT. Validation of an indirect calorimeter to
                                                                           measure oxygen consumption in critically ill patients. Journal
DO2 may actually decrease plasma concentrations of
                                                                           of Critical Care 1991; 6: 36–41.
lactate and that transplantation outcome could be                    18.   Takala J, Keinanen O, Vaisanen P, Kari A. Measurements of
modified by decreasing plasma lactate concen-                              gas exchange in intensive care: laboratory and clinical
trations. Further studies are required to confirm this                     validation of a new device. Critical Care Medicine 1989; 17:
hypothesis.                                                                1041–1047.
                                                                     19.   Ronco JJ, Fenwick JC, Tweeddale MG, Wiggs BR, Phang
                                                                           PT, Cooper DJ, Cunningham KF, Russell JA, Walley KR.
Acknowledgements                                                           Identification of the critical oxygen delivery for anaerobic
                                                                           metabolism in critically ill septic and nonseptic humans.
We thank G. Annat, Professor of Physiology, Hôpital E. Herriot,            Journal of the American Medical Association 1993; 270:
Lyons, France.                                                             1724–1730.
                                                                     20.   Mira JP, Fabre JE, Baigorri F, Coste J, Annat G, Artigas A,
                                                                           Nitenberg G, Dhainaut JFA. Lack of oxygen supply de-
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