Effects of phentolamine on tissue perfusion in pediatric cardiac surgery

Effects of Phentolamine on Tissue Perfusion in Pediatric Cardiac Surgery £)zge K6ner, MD, Serap Tekin, MD, Ali K6ner, MD, Nerime Soybir, MD, Sinan Seren, MD, and Kamil KaraoOlu, MD Objective: To evaluate whether the deleterious effects of cardiopulmonary bypass (CPB) can be overcome by phentolamine-induced pharmacologic vasodilation in pediatric patients with congenital heart disease. Design: Prospective, randomized, clinical study. Setting: Single university hospital. Participants: Forty-three pediatric patients undergoing open cardiac surgery for repair of congenital heart disease. Interventions: Patients were randomly allocated into two groups. Patients in group 1 (n = 22) received 0.2 mg/kg of phentolamine during the cooling and rewarrning periods of CPB. Group 2 patients (n = 21) did not receive phentolarnine. Temperature measurements (rectal [R], nasopharyngeal [N], and toe [P]) and serum lactate values were obtained before, during, and after CPB; systemic oxygen consumption was evaluated during CPB. Measurements and Main Results: At the end of the CPB period and at the end of the operation, lactate values of group 1 (1.87 ± 0.37 and 1.8 ± 0.39 rnmol/L, respectively) were significantly lower than values of group 2 (2.24 ± 0.28 and 2.33 ± 0.33 rnrnol/L; p < 0.05 and p < 0.05, respectively). At the beginning of the rewarrning period N-R temperature gradients of group I (0.14°C ± 0.920C) were lower than group

2 (-0.58"C ± 1.84"C) values (p < 0.05). Central-peripheral temperature gradients of group 1 obtained at the end of the CPB period (N-R = 2.18°C ± 0,690C; N-P = 7.84°C ± 1.54°C; R-P = 5.66°C ± 1.70,C) were significantly lower than the values of group 2 (N-R = 2.80°C ± 0.910C, N-P = 9.97°C ± 2.02°C; R-P = 7.18°C ± 2.100C; p < 0.05; p < 0.001; p < 0.05). At the end of the operation values of group I (N-R = 0.48°C ± 0.31°C;N-P = 6.30°C -+ 1.23°C; R-P = 5.82°C ± 1.160C} were significantly lower than the values of group 2 (N-R = 0.940C ± 0.560C; N-P = 8.6g*c ± 0.28"C; R-P = 7.75°C ± 2.15"C; p < 0.05; p < 0.001; p < 0.001). The systemic oxygen consumption values of group 1 were higher than group 2 (6.26 ± 1.82 v 5.17 ± 1.05 rnL/rnin/kg; p < 0.05) after complete rewarrning. Mean arterial pressure (MAP) values of group 1 (58.9 ± 6.4 mmHg} were lower than group 2 (63.4 ± 6.7 rnrnHg) at the period after CPB (p = 0.03). Conclusion: The results suggest that the use of phentolamine during CPB is associated with limited systemic anaerobic metabolism and more uniforrn body perfusion.

A R D I O P U L M O N A R Y BYPASS (CPB) and hypothermia affect most of the body's physiologic processes. Some of these effects are controlled completely or at least partially during or after CPB, but some are out of direct control. An example of the latter group is the systemic inflammatory response induced by the contact of blood with nonendothelial foreign surfaces.1 Partially controllable parameters are systemic vascular resistance, total-body oxygen consumption, regional and organ blood circulation, metabolic rate, and lactic acidosis. The effects of completely controllable parameters, such as blood flow rate and pattern, perfusion temperature, perfusate characteristics, and systemic arterial, venous, and pulmonary pressures, have been widely investigated and clarified. Nevertheless, it is evident that ideal CPB management can only be accomplished by attaining optimum physiologic parameters that are now uncontrollable or partially controllable. These effects are among the principal causes of increased morbidity, especially in infants and children undergoing cardiac surgery. 2,3 In this study, the authors investigated whether the negative effects of CPB on pediatric patients' arterial tone and microcirculation can be overcome by pharmacologic vasodilation. Therefore, the effects of intravenous phentolamine (Regitine; Ciba-Geigy, Basel, Switzerland) on body heat distribution, oxygen consumption, and blood lactate values were assessed during and after CPB.

PATIENTS AND METHODS

All patients were premedicated with intramuscular midazolam, 0.2 mg/kg, and morphine chloride, 0.03 mg/kg, 20 minutes before surgery. Anesthesia was induced with fentanyl, 25 ~g/kg, pancuronium, 150 btg/kg; midazolam, 0.1 mg/kg; and oxygen-air mixture. Fentanyl infusion, 0.3 pg/kg/min (up to a total dose of 100 ~tg/kg); pancuronium, 0.05 mg/kg at the onset and termination of CPB; midazolam boluses, 0.1 mg/kg as needed; and 50% oxygen in air were used for maintenance of anesthesia. Mechanical ventilation was provided by a Servo 900 C (Siemens-Elema, Solna, Sweden) throughout the operations. Volumecontrolled ventilation was started with 10 mL/kg tidal volumes and then adjusted to maintain PaCO2 between 30 and 35 mmHg. Respiratory frequency was adjusted according to the patients' age. The arms were kept tucked to the patient's side and covered with cloths to minimize heat loss throughout the operations. The operating room ambient temperature was maintained between 20°C and 22°C during the rewarming phase of CPB, and warming blankets were used concurrently (Blqakqdar, istanbul, Turkey). In all patients, a median stemotomy was performed. CPB was initiated after standard aorta-bicaval cannulation. A membrane oxygenator (Minimax Plus; Medtronic Inc, Anaheim, CA) and a nonpulsatile roller pump (model 10.10.00; St6ckert Instruments; Munich, Germany) were used. Venting of the left heart was performed with a left atrial vent inserted through a small incision at the interatrial septum or an open foramen ovale or atrial septal defect, if present. Priming fluids consisted of isotonic sodium chloride supplemented with heparin; mannitol, 0.5 mg/kg; methylprednisolone, 30 mg/kg; and aprotinin, 30 KIU/kg. Fresh whole blood was added to the priming solution in appropriate amounts to achieve a hematocrit of 20% to 22% during CPB. Moderate hypothermia (26°C to 28°C) was used during CPB. Pump flows were 2.4 to 2.6 L/min/m2 during the normothermic period. When the

After approval by the ethics committee, the authors studied 43 patients undergoing CPB for congenital heart disease repair between November 1994 and December 1995. Patients aged 0 to 6 years were randomly allocated into two groups using computer-generated random numbers. Group I and group 2 consisted of 22 and 21 patients, respectively. Patients undergoing reoperations, deep hypothermia, patients with low cardiac output (CO) and nonpalpable peripheral pulses preoperatively (eg, accompanying coarctation of the aorta) were excluded from the study.

From the Department of Anaesthesiology and Intensive Care, Cardiology Institute of lstanbul University; and the Department of Cardiovascular Surgery, Deutches Krankenhaus, lstanbul, Turkey. Address reprint requests to Ozge KOner, MD, Gedikli sokak, Vehbi Aytan apt. No 31/3, 81040, Ktztltoprak, lstanbul/Tiirkiye. Copyright © 1999 by W.B. Saunders Company 1053-0770/99/1302-0015510. 00/0

C

Journal of Cardiothoracic and Vascular Anesthesia,

Copyright © 1999 by W.B. Saunders Company KEY WORDS: phentolamine, tissue perfusion, extracorporeal circulation, pediatric cardiac surgery

Vo113,No 2 (April),1999:pp 191-197

191

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KONER ET AL

nasopharyngeal temperature reached 26°C to 28°C, pump flows were kept at 1.8 to 2 L/mirdm2. Vasoconstrictor agents were not used to increase perfusion pressure; mean arterial pressure (MAP) was maintained by CPB flow adjustments, as needed. At the beginning of the rewarming period, pump flows were adjusted to normothermic values again. The rewarming period was accomplished when the nasopharyngeal temperature reached 37.5°C. The temperature of the warming blanket placed under the patients was adjusted to 37°C to 38°C. During the cooling and rewarming periods, the temperature difference between the arterial perfusate and water bath circuit was kept at 8°C to 10°C. Isothermic blood cardioplegia with 25 mEq/L of potassium (20 mL/kg for induction) was injected into the aortic root after aortic crossclamping. This was followed by 10 mL/kg every 20 minutes during aortic cross-clamping, and throughout this period, topical myocardial cooling was used. Acid-base status and blood gases were adjusted according to e~-stat method during CPB. Hematocrit values were kept between 20% and 25% during the hypothermic phase and 30% during the rewarming period of CPB. Dopamine infusions, if needed in the postbypass period, were kept to a rate less than 6 pg/kg/min, and the occasional patients who required additional inotropic support received an epinephrine infusion in a dose not exceeding 0.03 gg/kg/min. MAP and heart rates (HRs) were recorded throughout the operation and the following 24 hours in the intensive care unit (ICU). All the patients were transferred to the ICU under deep anesthesia and controlled ventilation. Sedation was continued in the ICU until the patients reached hemodynamic stability. All group 1 patients were administered systemic phentolamine, 0.2 mg/kg, at the beginning of the cooling and rewarming period on CPB. None of the group 2 patients was administered phentolamine. The patients' body temperature distribution and lactate production were assessed before, during, and after CPB. Oxygen delivery (DO2) and oxygen consumption (VO2) values were calculated throughout the CPB period in order to compare effectiveness of body perfusion. A sampling schedule is shown in Figure 1. Rectal (R), nasopharyngeai (N), and peripheral toe (P) temperatures were monitored continuously throughout the study using a temperature monitor (Siemens Sireeust 404-1, Solna, Sweden). The temperatures were recorded during anesthesia induction, at the beginning of CPB, just before rewarming, at the end of CPB, and at the end of the operation. For all patients, N-R, N-R R-P temperature differences were recorded and both groups were comp~Yed according to these differences. During CPB, arterial and venous blood samples were obtained every 20 minutes, for hemoglobin and blood gas analysis. The hemoglobin and blood gas analysis were assessed with a Radiometer ABL-510 (Copenhagen, Denmark). According to this analysis, arterial-venous

Temperature

•

•

Oxygen Consumption Lactate

•

•

oxygen contents, oxygen delivery, and oxygen consumption values were calculated. The following calculations were recorded: At the beginning of the CPB, at the end of the cooling period, at the beginning of the rewarming, the 15th minute of rewarming, and at the end of CPB. Whole-body oxygen consumption was calculated by the Fick equation from the arterial pump flow and the arteriovenous oxygen content difference. VO2 values were divided by body weights of patients, values per kilogram were obtained, and group results were compared with each other. Arterial blood samples were drawn four times to assess the serum lactate values: During anesthesia induction, at the end of the cooling period, at the end of the CPB, and at the end of the operation. Assessments were accomplished by fluorescent polarization immunoassay method with the TDx analyzer (Abbott Lab, Wiesbaden, Germany). Aortic cross-clamping, duration of total bypass, open sternotomy periods, and the duration of the operation, intubation, and intensive care periods were recorded. Data are presented as mean values with standard deviations. The results were analyzed using the Student t test, the Bonferroni test, and the chi-squared test where appropriate according to data distribution. Statistical significance was assumed to have a p value of less than 0.05.

RESULTS

T h e d e m o g r a p h i c , operative, postoperative, a n d pathologic data o f the patients did n o t s h o w statistical significance b e t w e e n the g r o u p s (Tables 1 and 2). N-R, N-P, R - P t e m p e r a t u r e difference v a l u e s obtained during a n e s t h e s i a i n d u c t i o n at the b e g i n n i n g o f C P B did n o t s h o w statistically significant differences b e t w e e n the groups. N-P, R - P t e m p e r a t u r e difference values obtained at the b e g i n n i n g of the r e w a r m i n g in g r o u p 1 and 2 did n o t s h o w a statistical difference b e t w e e n the groups. In the s a m e period, N - R v a l u e s o f g r o u p 1 a n d 2 were respectively 0.14 + 0.92°C v e r s u s - 0 . 5 8 + 1.84°C a n d the difference w a s statistically significant ( p < 0.05). A t the e n d of the CPB, a s s e s s m e n t s o f group 1 were N-R: 2.18 _+ 0.69°C, N-P: 7.84 _+ 1.54°C, R-P: 5.66 -+ 1.70°C a n d o f g r o u p 2 were N-R: 2.8 +_ 0.91°C. N-P: 9.97 _+ 2.02°C and R-P: 7.18 -4- 2.10°C. T h e t e m p e r a t u r e difference values were significantly lower in the first group ( p < 0.05). A t the e n d o f the operation, values o f group 1 were respectively N-R: 0.48 + 0.31°C, N-P: 6.30 -+ 1.23°C, R-P: 5.82 + 1.16°C, and values o f group 2 were N-R: 0.94 _+ 0.56°C;

•

•

•

•

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8 m~

LU

C)

~ m~ CO

w

Fig 1. "timing of temperature recordings and blood retrievals for oxygen consumption and serum lactate analyses.

EFFECTS OF PHENTOLAMINE ON TISSUE PERFUSION

193

Table 1. Demographic and Durational Data of Patients

Age (Mo) Sex Male Female Weight (kg) Body surface area (m 2) Aortic cross-clamp time (rain) Duration ofCPB (min) Open sternotomy period (min) Intubation period (hrs) Stay in ICU (hrs) Mortality

Group 1 (Phentolamine)

Group 2 (Control)

21 ± 17

26 ± 15

13 9 8.80 ± 2.82 0.42 ± 0.1 69 ± 14 103 ± 24 162 ± 40 31.2 ± 28.9 97.7 ± 51.6 0

8 13 10.18 ± 2.59 0.47 ± 0.1 62 ± 20 102 ± 33 160 ± 38 28.6 ± 28.9 112.3 ± 110.5 0

Table 3. Comparison of Patients' Nasopharyngeal, Rectal, and Peripheral Temperature Differences

p Values*

>0.1 >0.1 >0.1 >0.1 >0.1 >0.1 >0.1 >0.1

N-P: 8.69 -+ 0.2°C, R-P: 7.75 _+ 2.15°C. Temperature gradients of the first group were significantly lower than the second group's values (p < 0.05). Temperature gradient data are presented in Table 3; correlation among N, P, R temperatures is presented in Figure 2. Oxygen consumption calculations per kilogram made at the beginning of CPB, at the end of the cooling period, at the beginning of the rewarming period, and 15 minutes after the beginning of the rewarming did not show a statistical difference between the groups. At the end of the CPB, oxygen consumption values of groups 1 and 2 were 6.26 - 1.82 mL/n~n versus 5.17 - 1.05 mL/min. The VO2 values of the first group were higher than the second group and the difference between the two groups was statistically significant (p < 0.05). VO2 data are presented in Table 4 and its change during CPB is presented in Figure 3. There was no statistical difference between the two groups' lactate values obtained during anesthesia induction and at the end of the cooling period of CPB. Lactate values of groups 1 and 2 obtained at the end of the CPB were respectively 1.87 --Table 2. Pathologic Data of the Groups

TOF VSD (ASD) (PDA) (PS) (ASD and subaortic stenosis) (Mitral valve insufficiency) Atrioventricular canal defect TAPVC DORY, VSD, PDA, and RVOT ASD Congenital mitral valve disease Pulmonary hypertension

Group 1 Group 2 ( P h e n t o l a m i n e ) (Control) 8 8 (2) (1) (1) (1) 2 2 1

9 3

(2)

(1) 7 1 1

1 6

Group I (Phentolamine) Anesthesia induction Nasopharyngeal-rectal

NOTE. Values are expressed as mean ± SD. *Chi-squared test or Student ttest where appropriate.

Pathology (Additional P a t h o l o g y )

Temperature Gradient (°C)

>0.1 >0.1

7

Abbreviations: TOF, Tetralogy of Fallot; VSD, ventricular septal defect; ASD, atrial septal defect; PDA, patent ductus arteriosus; PS, pulmonary stenosis; TAPVC, total anomalous pulmonary venous connection; DORV, double outlet right ventricle; RVOT, right ventricle outflow tract obstruction.

Nasopharyngeal-peripheral

0.63 ± 0.53 7.61 ± 1.43 6.99 ± 1.46

Group 2 (Control)

p*

0.76 ± 0.67 >0.1 7.03 ± 2.21 >0.1 6.27 ± 1.82 >0.1

Rectal-peripheral Beginning of CPB Nasopharyngeal-rectal -0.40 ± 1.01 -0.10 ± 1.03 >0.1 Nasopharyngeal-peripheral 6.17 ± 1.41 5.60 ± 1.96 >0.1 Rectal-peripheral 6.58 ± 1.29 5.60 ± 2.02 >0.05 Beginning of rewarming period Nasopharyngeal-rectal 0.14 ± 0.92 -0.58 + 1.84 <0.05 Nasopharyngeal-peripheral 1.19 ± 1.51 0.70 ± 1.36 >0.1 Rectal-peripheral 1.27 ± 1.28 1.30 ± 1.48 >0.1 End of the CPB Nasopharyngeal-rectal 2.18 ± 0.69 2.80 _+ 0.91 <0.06 Nasopharyngeal-peripheral 7.84 ± 1.54 9.97 ± 2.02 <0.001 Rectal-peripheral 5.66 ± 1.70 7.18 ± 2.10 <0.05 End of the surgery Nasopharyngeal-rectal 0.48 ± 0.31 0.94 ± 0.56 <0.05 Nasopharyngeal-peripheral 6.30 ± 1.23 8.69 ± 2.28 <0.001 Rectal-peripheral 5.82 ± 1.16 7.75 ± 2.15 <0.001 NOTE, Values are expressed as mean ± standard deviation. *Student ttest.

0.37 mmol/l_, versus 2.24 _-+ 0.28 mmol/L. At the end of the operation, these values were 1.8 - 0.39 mmol/L vs. 2.33 -+ 0.33 mmol/L and the statistical difference between the two groups was significant (p < 0.05). The lactate values of both groups are shown in Table 5 and the lactate values are shown in Figure 4. Except for the MAP values obtained in the post-CPB period, the mean values of MAP and HR of both groups recorded throughout the operation and ICU periods did not show statistical significance. MAP values of group 1 (58.9 -.+ 6.4 mmHg) obtained in the post-CPB period were lower than group 2 (63.4 __- 6.7 mmHg). The difference was statistically significant (p < 0.05). MAP and HR values of both groups are shown in Table 6. Postoperative pulmonary hypertensive crisis occurred in three patients in the control group, low CO was observed in one of these patients. One patient had laryngeal strider in the study group postoperatively, which did not affect respiratory functions. All the patients recovered completely. DISCUSSION

During the hypothermia and CPB periods, different tissues of the body show variable amounts of vasoconstriction and arteriovenous shunting. These physiologic changes result in tissue hypoperfusion, shunting of the arterial blood into the venous system without delivering sufficient oxygen and substrates, nonuniform cooling and rewarming of the body, and accumulation of metabolic intermediates. These metabolic intermediates create an additional stress on the organism during the critical period after CPB. 4,5 It was thought that increased endogenous catecholamine levels are principally responsible for these changes. 6 Phentolamine is an a-adrenergic blocking

194

KONER ET AL

10

<0.05

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-& A

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6

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ae6~.~ of Rewanning

end of CPIB

e.d of Operation

Fig 2. Correlation among nasopharyngeal (N), rectal (R) and peripheral (P) temperatures during the surgery. O, N-R (Phentolamine); II, N-P (Phentolamine); &, R-P (Phentolamine); <>, N-R; I-1 N-P.

agent that can antagonize the vasoconstriction produced by catecholamines. During the past 3 decades, a significant amount of research has been conducted on methods for preventing undesired effects of CPB either by the use of pharmacologic agents or by enhancing CPB techniques. 7-11For this purpose, many investigators examined heat distribution between tissues, as well as lactate production and oxygen consumption as indicators of tissue perfusion. In the authors' study, these variables were evaluated together to determine the effects of pharmacologic vasodilation on the relation between perfusion and metabolism. Ideal inspection of the heat distribution between various tissue groups requires complex monitoring techniques that are difficult to accomplish under clinical conditions. For this Table 4. Comparison of the Groups According to VO= Values VO~Jbodyweight (mL/min/kg) Group 1 (Phentolamine) Beginning of CPB End of the cooling Beginning ofthe rewarming 15th minute of the rewarming End of the CPB

4.06 2.69 3.14 6.10 6.26

± ± ± ± ±

1.54 1.35 1.36 2.66 1.82

NOTE. Values are expressed as mean ± SD. *Student ttest.

Group 2 (Control) 4,31 2,68 3.70 5,59 5.17

± ± ± ± ±

1.27 1.08 1.23 1,46 1.06

pValue >0.1 >0.1 >0.1 >0.1 <0.06

reason, in clinical practice, temperature measurements were made at specific sites of the body to give an approximation of the temperature of specific tissue groups. Nasopharyngeal and esophageal temperatures were used as indicators of the central temperature during cardiac surgery. Experiments have shown that during the cooling and rewarming periods of CPB, the esophageal and nasopharyngeal temperatures change rapidly and parallel to each other. 12A3However, when the chest is open, esophageal temperature may not reflect the central temperature accurately. Because of this, in the authors' study, nasopharyngeal temperature was preferred as an indicator of central temperature. Rectal temperatures are routinely monitored during CPB to assess the completeness of cooling and rewarming. 14 In the pediatric patient group, rectal temperature mostly reflects peripheral temperature. In the authors' study group, which consisted of pediatric patients, rectal temperature was evaluated as a third temperature parameter. A study by Bridges et al7 showed that the temperature of the foot was more sensitive than the temperature of the hand. Another study revealed that for anatomic or physiologic reasons, temperature gradients in the toes develop more readily than those in the fingers. 15 At the beginning of the rewarming period, when the phentolamine group of patients' nasopharyngeal and rectal temperatures were almost equal, the control group patients' rectal temperatures were higher than the nasopharyngeal temperatures. This difference, which shows statistical significance, was due to the

EFFECTS OF PHENTOLAMINE ON TISSUE PERFUSION

195

p < 0.05

6

5,

2

i ii

Fig 3. Change of oxygen consumption values during CPB for both groups. II, group 1; r-i group 2.

Beginning of CPB

End of Cooling

homogenous body cooling effect of phentolamine given during the hypothermic period. In contrast, in the control group, central cooling was not rapidly accompanied by the whole body mass. Calculations made at the end of the CPB and the surgery showed that in the phentolamine group patients' N-R, N-P, and R-P temperature differences were significantly lower than the control group. These findings suggest that phentolamine use during the operative period facilitates central heat distribution to the whole body and may help provide higher peripheral temperatures and lower temperature differences between tissues. As the oxygen consumption values are examined, the first four sets of calculations provided similar results for the two patient groups. Calculations made at the end of the CPB indicate that in the phentolamine group, oxygen consumption values were significantly higher than in the control group. It should be carefully discussed whether this increase in VO2 implies that phentolamine provides better tissue perfusion or Table 5. Comparison of Two Groups" Perioperative Serum Lactate Values Lactate (mmol/L) Group 1 (Phentolarnine) Anesthesia induction End of the cooling End of the CPB End of the surgery

1.38 1.75 1.87 1.80

_+ 0.43 ± 0.37 ± 0.37 ± 0.39

Group 2 (Control) 1.58 1.82 2.24 2.33

± ± _ ±

0.45 0.38 0.28 0.33

p* >0,1 :>0.1 <0.05 <0,001

NOTE. Values are expressed as mean _+ standard deviation. *Student ttest.

Beginning of Rewarming

16 Minute Rewarming

End of CPB

not, because the VO2 values obtained only make sense if the real oxygen needs of the tissues are known and to what extent these needs are fulfilled. Nevertheless, the oxygen demand of the organs, the tissues or the whole metabolism cannot be measured directly. Investigations show that in standard conditions, the amount of oxygen to be consumed was directly determined by the body's own needs and was not affected by the fluctuations in DO2, unless DO2 falls below a critical level. 16,17 Below the critical level, VO2 is directly proportional to DO2 or to the blood circulation. This decrease is accompanied by anaerobic metabolic conditions, lactic acid production, and tissue injury. Therefore, a decrease in tissue VO2 is viewed as a marker of inadequate oxygenationJ 8 In light of this information, observation of high oxygen consumption values after CPB in patients who were given phentolamine may be explained in two different ways: (1) Oxygen supply to various parts of the body, which is reduced during CPB, is altered by means of the better perfusion provided by phentolamine, so that the overall oxygen demand of the body can be met to a greater extent leading to increased oxygen consumption. This explanation is acceptable provided that the real oxygen requirement is assumed to be equal in the two patient groups. (2) At the end of CPB, a higher peripheral temperature and a more homogenous rewarming were obtained by the use of phentolamine. An increased oxygen need because of these changes may be the cause of the rise in the oxygen consumption. In addition to the oxygen requirement of the tissues, ability of oxygen extraction was increased parallel to the temperature. In this case, it can be emphasized that although a higher oxygen level was not supplied, the use of phentolamine

196

KONER ET AL 2.5

p < 0.001 0

E E

•- " b3

1.5

=, 0 = --I

1

E 2 0 t./) 0.5

Induction

End of Cooling

End of CPB

provided a more balanced rewarming and a more homogenous distribution of perfusion, which led to a better extraction of oxygen. Stronger data concerning to what extent the oxygen need was met can be obtained by the evaluation of anaerobic metabolism. For this purpose, lactate measurements were carded out parallel to the oxygen consumption measurements. The lactate levels in both patient groups were found to be similar during the anesthesia induction and the CPB periods. At the end of the CPB period, an increase in the lactate level in patients who did not receive phentolamine was noticeable. At the end of the operation this increase was more prominent. Dantzker19 defined this phenomenon as a "gold standard" for the evaluation of insufficient tissue perfusion. The amount of lactate in the blood circulation was determined by many variables that affect the production of this metabolite as well as its removal from the tissues. The primary cause of the lactate increase is its release from tissues to the circulation. Evaluation of the oxygen consumption and lactate levels showed that at the end of the CPB period, the oxygen consumption was inversely proportional to the lactate levels in patients not receiving phentolamine, but normal lactate levels were maintained while the oxygen consumption levels rose during rewarming in the phentolamine group patients.

End of Operation

Fig 4. Comparison of serum lactate values during the surgical period. II, group 1; [~, group 2.

Considering the relationship between the high mortality rate and serum lactate levels exceeding 2.5 to 3 mmol/L, it might be concluded that the use of phentolamine provides a more physiologic circulation during CPB. The most evident periods of insufficient tissue perfusion are the cooling and rewarming periods. Anaerobic metabolic activity reaches its maximum value while the serum lactate level is only slightly increased in the hypothermic period. A sharp increase in the lactate level after rewarming could be explained by the tissue perfusion conditions during CPB. Lactic acid accumulated in the tissues due to inadequate blood flow during hypothermia, therefore sequestrated from the systemic circulation, is released into the blood after the reopening of the microcirculation area through rewarming. In patients receiving phentolamine, increasing lactate levels at the end of the CPB period show a steady state toward the end of the surgery, whereas it continues to rise in patients who did not receive phentolamine. These findings suggest that the use of phentolamine does not only limit the lactic acid production during the hypothermic period, but also aids the disposal of lactic acid from tissues. Seelye et al called the physiologic state after hypothermia the "oxygen debt repayment" period in infants.2° In the authors' study, the oxygen consumption observed at the end of the CPB, which showed a

Table 6, Hemodynamic Data MAP (mmHg)

Pre-CP6

CPB

Post-CPB

Group 1

65 -+ 7.9

48.4 ± 6.6

58.9 -+ 6.4*

Group 2

65.9 -+ 7.7

52.5 ~ 8.9

63.4 _+ 6.7

NOTE. Values

are expressed as mean _+ standard deviation.

* p < 0.05 w h e n compared w i t h g r o u p 2.

HR (per minute)

ICU

Pre-CPB

Post-CPB

69 -- 6.9

124.2 + 14.5

143.8 -+ 14

68.6 -+ 5.8

123.3 ± 16.5

139.5 ± 12.7

ICU 138.2 + 13.4 142 ± 11.9

EFFECTS OF PHENTOLAMINE ON TISSUE PERFUSION

197

remarkable rise compared with the beginning period, might be accepted as a good indicator of the efficiency of this repayment. A variety of vasodilator agents have been studied for their effects on tissue perfusion during CPB. Research comparing sodium nitroprusside to isoflurane shows that isoflurane has similar effects to sodium nitroprusside as well as providing more stable hemodynamics. 21 A controlled study conducted in previous years showed that sodium nitroprusside causes a drastic fall in arterial pressure without altering the oxygen consumption and blood lactate levels.l° This is partly due to the fact that sodium nitroprusside, which differs from phentolamine in the vasodilation mechanism involved, helps reopen arteriovenous shunts that are not used for tissue perfusion instead of changing the microcirculation to facilitate the blood flow to ischemic tissues.

Due to the difficulty of using more precise and specific techniques in evaluation of the perfusion state of the isolated organs and tissues in the clinical setting, the authors' study was limited to the evaluation of systemic parameters that provide a rough idea concerning the global perfusion quality of the whole organism. In conclusion, data obtained in this study showed that administration of phentolamine during CPB leads to more uniform heat distribution, diminished lactate levels, and increased oxygen consumption in pediatric patients undergoing cardiac surgery. These findings may be interpreted as an improvement in tissue perfusion by the use of phentolamine during CPB. Further clinical studies are needed to investigate the short-term and long-term postoperative course after the use of phentolamine.

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