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Pharmacological vasodilatation improves efficiency of rewarming

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					British Journal of Anaesthesia 1998; 81: 147–151

Pharmacological vasodilatation improves efficiency of rewarming from
hypothermic cardiopulmonary bypass

                                                          Pharmacologically-induced vasodilatation has been
Summary                                                   proposed as a method to limit postoperative
An afterdrop in core temperature after hypother-          hypothermia6 by improving rewarming of constricted
mic cardiopulmonary bypass (CPB) is related to            vascular beds. In this previous study, pharmacologi-
inadequate peripheral rewarming. We proposed              cal vasodilatation was combined with increased
that     pharmacological     vasodilatation during        pump flow, and therefore increased heat delivery to
rewarming on bypass would improve peripheral              ths patient, so that the contribution of each factor to
rewarming and reduce the degree of afterdrop.             the subsequent reduction in postoperative hypother-
Fifty-nine of 120 patients were randomized to             mia was unclear. This study was designed to deter-
receive a sodium nitroprusside (SNP) infusion             mine whether pharmacological vasodilatation alone
during the rewarming stage of hypothermic                 during the rewarming phase of hypothermic CPB
CPB. Mean systemic vascular resistance (SVR)              would improve the efficiency of rewarming and
during the rewarming phase of CPB was                     reduce postoperative hypothermia.
1129 dyne s91 cm95 in the control group and
768 dyne s91 m95 in the SNP group (P 0.001).
Patients receiving SNP rewarmed to 37.0 C                 Patients and methods
faster (299 min vs 376 min; P:0.003) and were             After obtaining local Ethics Committee approval,
extubated earlier (490 min vs 621 min; P:0.001).          120 sequential patients undergoing elective first-time
Patients receiving SNP had a warmer mean                  coronary artery bypass grafting or valve replacement,
peripheral temperature (MPT) (32.9 C vs 32.4 C;           or both, were entered into the study after written
P:0.05) on termination of CPB. Postoperative              informed consent. Patients with peripheral vascular
core temperature fell less in the SNP group               disease, diabetes mellitus or those subsequently
(35.6 C vs 35.2 C; P:0.01) as did MPT (31.8 C vs          returning to theatre for operation were excluded.
31.2 C; P:0.004). SNP-induced vasodilatation              Using a binary random number generator, patients
during    rewarming     from    hypothermic  CPB          were randomly assigned to a control group or to
improves peripheral rewarming, reduces the                receive sodium nitroprusside (SNP). SNP was
degree of postoperative core and peripheral               administered via a syringe driver (Graseby 3400)
hypothermia and reduces time to extubation. (Br.          from the start of rewarming on CPB to the termina-
J. Anaesth. 1998; 81: 147–151)                            tion of CPB at a rate adjusted manually to give a
                                                          mean arterial pressure (MAP) of 40 mm Hg. MAP
Keywords: surgery, cardiopulmonary bypass; hypothermia;
sodium nitroprusside
                                                          during rewarming in the control group was not
                                                          adjusted other than to maintain MAP below 80 mm
                                                          Hg using 1-mg increments of phentolamine as is our
During hypothermic cardiopulmonary bypass
                                                          usual practice. Patients receiving SNP did not receive
(CPB), core temperature is usually reduced to below
                                                          inotropic or vasoconstrictor agents concurrently.
30 C to reduce tissue oxygen consumption and
                                                          Peri-operative management was otherwise identical
afford some degree of cerebral and myocardial pro-
                                                          in both groups.
tection. Despite apparently adequate rewarming as
                                                             Patients received lorazepam 2 mg orally 2 h before
judged by a normal core temperature on termination
                                                          operation followed by morphine 5–10 mg i.m. and
of CPB, moderate postoperative hypothermia is
                                                          scopolamine 0.2–0.4 mg i.m. 1 h before surgery.
common.1 2 Morbidity from postoperative hypother-
                                                          Radial artery and peripheral venous cannulas were
mia includes increased time to extubation, increased
                                                          inserted under local anaesthesia. Anaesthesia was
myocardial work and oxygen consumption, impaired
                                                          induced using midazolam 0.02–0.05 mg kg91 i.v., fen-
coagulation,3 4 increased risk of wound infection and
                                                          tanyl 10–15 g kg91 i.v. and pancuronium 0.1 mg kg91
prolonged hospital stay.5 Postoperative hypothermia
                                                          i.v. The trachea was intubated and the lungs mechani-
cannot be explained by heat loss to the environment
                                                          cally ventilated using oxygen in nitrous oxide,
alone and is thought to result from a failure of heat
                                                          adjusted to maintain normocapnia. A heat and mois-
transfer to vasoconstricted peripheral tissues during
                                                          ture exchanger was placed in the breathing circuit. A
rewarming on CPB, with a subsequent shift of heat
from a warm core to a cold periphery.4 6 Increasing
blood flow to vascular beds by increasing pump flow       C. D. DEAKIN, MA, MRCP, FRCA; D. SMITH MD, FRCA, (Department of
during rewarming on bypass reduces the degree of          Anaesthetics); G. W. PETLEY, BSC, PHD, MINSTP, CPHYS, (Medical
                                                          Physics and Bioengineering); Southampton General Hospital,
postoperative hypothermia,7 but the resultant pres-       Tremona Road, Southampton SO16 6YD. Accepted for publica-
sure in the arterial cannula of the extracorporeal        tion: March 18, 1998.
circuit may cause mechanical damage to blood.                Correspondence to C. D. D.
148                                                                                    British Journal of Anaesthesia

central venous catheter was then inserted. Anaesthesia   minute was summated to give an instantaneous TEB.
was maintained using propofol 80–150 mg h91 and          TEB is thus zero at commencement of bypass,
isoflurane to 1.2% as necessary. Midazolam 4 mg and      becomes negative as the patient is cooled, and
pancuronium 4 mg were added to the pump prime            returns to a positive value as the patient is rewarmed
fluid.                                                   before termination of bypass.
   Core temperature was measured using a calibrated         Operating theatre and intensive care environments
tympanic membrane thermocouple temperature               were maintained at a stable state as allowed by the air
probe (Mallinckrodt, Northampton, UK) placed             conditioning. Operating theatre temperature was
before induction of anaesthesia after visually con-      maintained between 20–24 C and relative humidity
firming with an otoscope that the external auditory      between 38–50%. Temperature in the intensive care
meatus was free from wax. Peripheral temperature         unit was maintained between 22–25 C. No heating/
was recorded using four calibrated thermistors           cooling mattress was used during the operation. After
(Yellow Springs 400) placed on the chest wall, upper     bypass, all i.v. crystalloid, colloid and blood products
arm, thigh and calf before induction of anaesthesia.     were administered through a blood warmer heated to
Mean skin temperature (MST) was calculated using         37.8 C until core temperature reached 37 C.
a weighted equation as described by Ramanathan8:         Patients were covered by a standard hospital woollen
                                                         blanket and cotton sheet. No active postoperative
 MST=0.3 (chest wall+upper arm)+0.2 (leg+thigh)
                                                         warming was used.
All temperatures were recorded to a temperature log-        Adequacy of rewarming was assessed by recording
ger9 at 1-min intervals from induction of anaesthesia    the coldest postoperative core temperature, following
until postoperative core temperature had returned to     termination of CPB (fig. 1A) and the time for the
37.0 C.                                                  postoperative core temperature to return to 37 C
   The CPB unit incorporated a Dideco D703 (Sorin,       following afterdrop (fig. 1B). Time rewarming on
Italy) hollow fibre membrane oxygenator with inte-       bypass was the time from the start of rewarming to
gral heat exchanger primed with lactated Ringer’s        the termination of CPB (fig. 1C). Time to extubation
solution. During hypothermic CPB, core tempera-          was the time from the end of bypass to extubation of
tures were reduced to 28–30 C. Pump flow during          the patient. The doctor deciding when to extubate
cooling and rewarming was adjusted according to a        the patient was blinded to the group to which the
standardized local procedure. Flow was indexed at        patient was allocated. Statistical analysis was per-
2.4 litre min91 m92 above 30 C, 1.8 litre min91 m92      formed with Microsoft Excel 5.0 using unpaired
between 28–30 C, and 1.2 litre min91 m92 below           two-way t tests. Results are given as mean values with
28 C, except during cooling when it was reduced to       confidence intervals (CI) for the mean difference
approximately 1.2 litre min91 m92. Rewarming aimed       between the control and SNP group. Significance
to restore the patients core temperature to 37 C         was taken as P 0.05.
before termination of CPB.
   Heat extracted and returned to patients whilst on
CPB was recorded using a previously described
energy balance machine.10 The apparatus comprised        One hundred and twenty patients were studied, of
an IBM compatible personal computer running ded-         whom 59 were randomly assigned to receive SNP.
icated software which interactively collects data from   There was no significant difference between control
a specifically designed energy flux measurement sys-
tem. The calculation of energy balance is based upon
the Pick principle using pump flow and arterial and
venous temperature in the perfusion circuit.
Net thermal energy balance (TEB) is calculated from
the equation:
              E=sp ∫0 (Ta9Tv) Q(t) δt
where: E:net thermal energy balance during CPB
(kJ), Q:pump flow at time t (litre min91), s:specific
heat capacity of blood (3.84 kJ kg91 C), p:density of
perfusate (approximately 1.0 kg litre91), a:arterial
infusion temperature ( C), Tv:venous infusion tem-
perature ( C), t:time.
   The temperatures of arterial and venous blood
were recorded at the inflow and outflow to the heat
exchanger/oxygenator unit using previously cali-
brated thermistor probes (Electromedics Inc,
Englewood CO 80112 USA, model No 4700
M344700) specifically adapted to fit the gold insu-
lated temperature probe ports on the inflow to the
heat exchanger (Tv) and the outflow from the oxy-        Figure 1 Core temperature changes during hypothermic
genator (Ta). Rotation of the pump was detected by       cardiopulmonary bypass. 1 : Induction; 2 : start of active cooling
an infrared reflective sensor placed over the pump       on cardiopulmonary bypass; 3 : stop active cooling; 4 : start
                                                         rewarming; 5 : separation from cardiopulmonary bypass.
head cover. As a marked limb passed beneath the          A : Coldest post-operative core temperature following termination
detector, the sensor registered one rotation equiva-     of CPB; B : time for the post-operative core temperature to return
lent to 46-ml volume. The energy flux measured each      to 37.0 C following the afterdrop; C : time rewarming on bypass.
Rewarming from cardiopulmonary bypass                                                                                149

and SNP groups in patient characteristics or environ-              thermal energy balance between control (805 kJ) and
mental conditions. Patient characteristics are given in            SNP groups (764 kJ) (95%CI -59.9 kJ to 141.7 kJ;
table 1. Ventilation was controlled manually for two               P:0.42), a power of 0.05 was insufficient to conclude
patients in the control group for a prolonged period               that this was a true negative result.
because of cardiovascular instability in one patient
and postoperative bleeding in the other. Time to
extubation of these patients was therefore excluded                Discussion
from the data. The power of the study was calculated               Our results showed that pharmacological vasodilata-
from the time to rewarm to 37 C in both groups.                    tion with SNP during the rewarming phase of CPB
Standardized difference was 0.564 giving a power of                rewarmed the patient more efficiently as shown by
0.87 using the nomogram described by Altman.11                     warmer peripheral temperatures on termination of
Mean arterial pressure during the rewarming phase                  bypass, suggesting that heat transfer to peripheral
of CPB was 53.5 mm Hg in the control group and                     vascular beds had been increased through increased
40.1 mm Hg in the SNP group (95%CI 10.8 to                         blood flow. The subsequent postoperative hypother-
15.9 mm Hg; P 0.001). This equates to a mean sys-                  mia was less in patients receiving SNP, shown by
temic vascular resistance (SVR) of 1129 dyne s91 cm95              greater postoperative minimum core and peripheral
and 768 dyne s91 cm95 respectively. There was no sig-              temperatures and shorter time to rewarm to 37 C.
nificant difference in the amount of perioperative i.v.            Clinically, improved rewarming resulted in earlier
fluid administered to the two groups.                              extubation.
   Time to rewarm to 37 C was 376 min in the con-                     Postoperative hypothermia is commonly seen in
trol group compared with 299 min in the SNP group                  patients after hypothermic CPB and is greater than
(95%CI 28 to 129 min; P:0.003). Time to extuba-                    that observed in patients undergoing thoracic opera-
tion was 621 min in the control group compared with                tions not requiring the use of CPB.12 Hypothermia
490 min in the SNP group (95%CI 70 to 232 min;                     during CPB causes intense vasoconstriction and
P:0.001).                                                          greatly reduces blood flow through peripheral vascu-
   Patients receiving SNP had a warmer MST on                      lar beds such as muscle and fat. During the rewarm-
termination of bypass (32.9 C) compared with the                   ing phase of CPB, the periphery is slow to warm
control group (32.4 C) (95%CI 0.06 to 0.94 C;                      because of the reduced blood supply to these vascular
P:0.05). There was no difference in core tempera-                  beds and the periphery remains relatively hypother-
ture on termination of bypass between the control                  mic when CPB is discontinued, despite attainment of
group (38 C) and SNP group (38.1 C) (95%CI -                       a normal core temperature.13 Once bypass is discon-
0.41 to 0.18 C; P:0.52).                                           tinued, the core temperature decreases as heat is
   Postoperative core temperature decreased further                transferred to the cold periphery. Evidence for this
in the control group (35.2 C) than the SNP group                   theory is growing.4 6 Pharmacological vasodilatation
(35.6 C) (95%CI 0.1 to 0.6 C; P:0.01). Minimum                     may force the periphery to vasodilate during rewarm-
postoperative peripheral temperature was warmer in                 ing, increase blood flow and heat transfer to the cold
the group receiving SNP (31.8 C) compared with                     peripheral tissues, thereby reducing the subsequent
control (31.2 C) (95%CI 0.14 to 0.90 C;                            decrease in core temperature.
P:0.004). Once postoperative core temperature had                     The use of vasodilatation during rewarming from
returned to 37.0 C, there was no difference in the                 hypothermia on CPB was first reported by Noback
core-peripheral temperature difference between the                 and Tinker.6 Twenty control patients were compared
control (3.65 C) and SNP groups (3.59 C) (95%CI                    with eight patients receiving SNP during rewarming
90.3 to 0.5; P:0.72).                                              on bypass. SNP was administered at a rate to main-
   There was no difference in time spent rewarming                 tain MAP       70 mm Hg as CPB pump flows were
on bypass between control group (30.6 min) or SNP                  increased. Increased CPB pump flow alone during
group (31.8 min) (95%CI -2.8 to 5.2 min; P:0.55).                  rewarming increases perfusion of muscle beds and
Bypass pump flows during rewarming were 8.4%                       reduces the degree of postoperative hypothermia.7
higher in the SNP group (control 3.92 compared with                Thus, although the study of Noback and Tinker
SNP 4.25 litre min91; 95%CI 0.17 to 0.48 litre min91;              reduced the degree of postoperative hypothermia,6
P:0.001). Although there was no difference in mean                 the relative contribution of increased heat delivery

            Table 1 Patient characteristics and environmental conditions.

                                                                              95% CI of mean difference
                                              Control group     SNP group     between groups              P

            Theatre temp. (°C)                22.2              22.3          90.20 to 0.37               0.64
            ITU temp. (°C)                    23.7              23.7          90.32 to 0.41               0.98
            Age (yr)                          65.7              64.0          92.40 to 5.81               0.41
            Weight (kg)                       71.9              77.0          90.2 to 10.4                0.06
            Height (cm)                       169.0             170.3         92.22 to 4.91               0.46
            Body mass index (kg m92)          25.1              26.4          90.01 to 0.14               0.09
            Body surface area (m2)            1.82              1.88          90.22 to 2.81               0.08
            Mean SNP dose ( g kg91 min91)                       1.40          <1.15 (SD)
            Rate of post-op. propofol
             infusion (ml h91)                13.2              13.2          90.97 to 1.14               0.87
            Cardioplegia volume (ml)          1227              1179          958 to 154                  0.37
150                                                                                         British Journal of Anaesthesia

and pharmacological vasodilatation is difficult to           postoperative rewarming have been unable to control
distinguish.                                                 ambient temperature more closely than our study6
   Aps, Hutter and Williams14 reviewed the postoper-         or do not report environmental conditions.20–22
ative progress of 143 cardiac surgery patients in            Environmental temperature did not show any signifi-
whom specific attempts to ensure adequate rewarm-            cant correlation with time to rewarm to 37 C or
ing on bypass had been made. Patients received infu-         coldest postoperative temperature.
sions of either SNP or glyceryl trinitrate (GTN) at a           By increasing peripheral blood flow, SNP adminis-
maximum rate that still allowed for adequate arterial        tered during rewarming on bypass appears to
perfusion pressures during rewarming on bypass               improve the efficiency of peripheral rewarming and
(details not given). Rewarming was further opti-             reduce the degree of postoperative hypothermia.
mized by the use of patient insulation, use of a warm-
ing mattress and heating of inspiratory gases to
40 C. Although this technique minimized the degree
of postoperative hypothermia, the relative contribu-         This work was funded in part by the Edith Powell and Geoffrey
tions of each technique cannot be distinguished.             Holt Research Awards from the British Medical Association
                                                             (1995). We thank Mr S. A. Livesey, Mr V. T. Tsang and Mr J. L.
   Both GTN and SNP have been used as peripheral             Monro for allowing us to study their patients, and the nursing staff
vasodilators in these earlier studies. Recent work sug-      in the Cardiothoracic Intensive Care Unit for their cooperation
gests that both GTN and SNP have similar arterio-            with the study.
venous vasodilatory profiles.15 SNP however was
chosen in preference to GTN for this study because
its greater potency and shorter half-life make it more       References
suitable for acute haemodynamic manipulation. SNP             1. Deakin C, Sewell A, Clewlow F, Pierce J. A comparison of
dilates large arteries,16 small arteries and arterioles,15       core temperature with thermal energy balance in predicting
                                                                 adequacy of rewarming from hypothermic cardiopulmonary
increases limb blood flow through vasodilatation of              bypass. British Journal of Anaesthesia 1996; 76: A41.
skeletal muscle vasculature17 and increases skin perfu-       2. Huang F, Wang M, Huang H. Differences in temperature
sion.18 SNP is not known to possess any thermogenic              changes between pediatric and adult patients after cardiopul-
properties.                                                      monary bypass. Journal of Cardiothoracic and Vascular
   By using the same rewarming plan for control and              Anesthesia 1993: 7: 66–68.
                                                              3. Baker J, Baker A, Mazer C. Determinants of postoperative
SNP groups, we hoped to achieve the same bypass                  hypothermia after normothermic cardiopulmonary bypass.
flow rates during rewarming in both groups.                      Journal of Cardiothoracic and Vascular Anesthesia 1995; 9:
Surprisingly, flow was 8.4% higher (P:0.001) in the              154–157.
SNP group. Although it may be expected that                   4. Pujol A, Fusciardi J, Ingrand P, Baudouin D, Le Guen A,
                                                                 Menu P. Afterdrop after hypothermic cardiopulmonary
increased flow would be associated with increased                bypass: The value of tympanic membrane temperature moni-
heat delivery (TEB) during rewarming to the SNP                  toring. Journal of Cardiothoracic and Vascular Anesthesia 1996;
group, the power of 0.05 for these data is insufficient          3: 336–341.
to distinguish any difference between the two groups.         5. Kurz A, Sessler D, Lenhardt R. Perioperative normotherrhia
Although the relative contribution of increased CPB              to reduce the incidence of surgical-wound infection and
                                                                 shorten hospitalization. Study of Wound Infection and
flow and vasodilatation to heat transfer cannot be               Temperature Group. New England Journal of Medicine 1996;
distinguished directly, the small difference in CPB              334: 1209–1215.
flow between our two groups and the differential              6. Noback C, Tinker J. Hypothermia after cardiopulmonary
changes in core–peripheral temperature in the SNP                bypass in man: amelioration by sodium nitroprusside induced
                                                                 vasodilation during rewarming. Anaesthesiology 1980; 53:
group leads us to believe that SNP was at least par-             277–280.
tially responsible for the observed differences.              7. Stanley T, Jackson J. The influence of blood flow and arterial
   In addition, the core temperature at the end of               blood pressure during cardiopulmonary bypass on deltoid
bypass was the same in both groups. We therefore                 muscle gas tensions and body temperature after bypass.
believe that the observed differences between the                Canadian Anaesthetists Society Journal 1979; 26: 277–281.
                                                              8. Ramanathan N. A new weighting system for mean skin tem-
control and SNP groups are attributable, at least in             perature of the human body. Journal of Applied Physiology
part, to the effects of pharmacological vasodilatation.          1964; 19: 531–533.
The larger differences in peripheral temperature              9. Petley G, Clitheroe S, Clewlow F, Deakin C, Chauhan A.
between the control and SNP groups observed by                   Development and application of a general purpose ambulatory
                                                                 monitor. Medical Engineering and Physics 1998; 20: 33–39.
Noback and Tinker6 may be caused by higher flows             10. Sansome A. Apparatus for the real-time calculation of thermal
enabling a higher rate of SNP infusion and a greater             energy flux during cardiopulmonary bypass. British Journal of
degree of peripheral vasodilatation.                             Hospital Medicine 1989; 42: 494.
   We avoided the use of warming blankets during             11. Altman D. Statistics and ethics in medical research: How large
rewarming from bypass and forced warm air convec-                a sample? British Medical Journal 1980; 281: 1336–1338.
                                                             12. Carli F, Aber V. Thermogenesis after major elective surgical
tion blankets postoperatively because vasodilatation             procedures. British Journal of Surgery 1987; 74: 1041–1045.
combined with active surface warming increases heat          13. Benson J, Patla V, Bonser R, Hutton P. Use of i.m. tempera-
transfer to the patient19 and may mask the effects of            ture probes during cardiopulmonary bypass in humans.
thermal energy redistribution in the body caused by              British Journal of Anaesthesia 1995; 75: 483–485.
                                                             14. Aps C, Hutter J, Williams B. Anaesthetic management and
the SNP infusion. Noback and Tinker used heating                 postoperative care of cardiac surgical patients in a general
mattresses during the rewarming phase of CPB in 16               recovery ward. Anaesthesia 1986; 41: 533–537.
of the 20 patients in the control group and 6 of the 8       15. MacAllister R, Calver A, Riezebos Jo, Collier J, Vallance P.
patients in the SNP group.6 They failed to show any              Relative potency and arteriovenous selectivity of nitrovaso-
difference between the two groups but this may be                dilators on human blood vessels: An insight into the target-
                                                                 ing of nitric oxide delivery. Journal of Pharmacology and
because of the small numbers in the study.                       Experimental Therapeutics 1995; 273: 150–160.
   Operating room and intensive care unit temperature        16. Komori K, Mawatari K, Itoh H, Sugimachi K. Impaired
varied by up to 4.0 C. Other studies investigating               vasodilation of peripheral arteries in response to acetylcholine
Rewarming from cardiopulmonary bypass                                                                                              151
    in human beings with abdominal aortic aneurysm. Journal of        20. Jenkins I, Karliczek G, Geus F, Brenken U. Postbypass
    Vascular Surgery 1994; 20: 803–807.                                   hypothermia and its relationship to the energy balance of car-
17. Steinberg H, Brechtel G, Johnson A, Fineberg N, Baron A.              diopulmonary bypass. Journal of Cardiothoracic and Vascular
    Insulin-mediated skeletal muscle vasodilation is nitric oxide         Anesthesia 1991; 5: 135–138.
    dependent. A novel action of insulin to increase nitric oxide     21. Jani K, Carli F, Bidstrup B, Royston D, Taylor K. Temperature
    release. Journal of Clinical Investigation 1994; 94: 1172–1179.       following cardiopulmonary bypass procedures; the effects of
18. Morris S, Shore A, Tooke J. Responses of the skin microcircu-         active rewarming. Life Support Systems 1986; 4: 269–272.
    lation to acetylcholine and sodium nitroprusside in patients      22. Davis F, Parimelazaghagan K, Harris E. Thermal energy
    with NIDDM. Diabetologia 1995; 38: 1337–1344.                         balance during cardiopulmonary bypass with moderate
19. Janke E, Pilkington S, Smith D. Evaluation of two warming             hypothermia in man. British Journal of Anaesthesia 1977; 49:
    systems after cardiopulmonary bypass. British Journal of              1127–1132.
    Anaesthesia 1996; 77: 268–270.