Effects body
of amino acid solution on temperature of patients
abdominal aortic
changes in undergoing
aneurysm
intraoperative surgery for
Yasuhiro Shiokawa, Jinsei Kouji
Oh, Masayuki Inamori, Hiromichi Hatta and Yoshihisa Koga
Kamamoto,
Department of Anesthesiology,
Osakasayama,
Kinki Osaka
University School of Medicine, 589-8511, Japan
Abstract
In this study, we compared the effectiveness of an amino acid solution and a second intra- venous solution containing glucose in preventing intraoperative hypothermia. Twenty patients undergoing scheduled surgery for abdominal aortic aneurysm were randomly divided into two groups of ten. The first group was given an infusion of amino acid solution, while the second was given acetated Ringer's solution with glu- cose. Each solution was administered over two hours after the induction of anesthesia, and intraoperative body temperature and blood glu- cose levels were measured. No significant change from preoperative levels was observed in either body temperature or blood glucose level
after 180 minutes in the group given the amino acid solution, and postoperative shivering did not occur. In contrast, there was a significant fall in body temperature in the group that received
acetated Ringer's solution with glucose, and postoperative shivering occurred. Blood glucose levels also rose significantly in the second group.
These results suggest that administration of amino acid solution following induction of anes- thesia is useful in preventing intraoperative hypothermia and postoperative shivering.
Key words : amino acid solution, acetated Ringer's solution, hypothermia, shivering, blood glucose, intraoperative management
Introduction
Patients undergoing highly invasive and pro- longed open abdominal surgery are prone to intraoperative hypothermia. It is known that patients who suffer from symptoms of hypother- mia, such as shivering, are particularly prone to postoperative complications, making intraoper- ative management of body temperature impor- tant. Use of warming equipment that uses warm air or water to prevent intraoperative hypother- mia is common, but may be inadequate depend- ing upon the type of surgery or condition of the patient ; however, amino acid solutions have been reported as effective in inhibiting falls in body temperature due to heat generated by the
metabolism of amino acids. Here we report our investigation of the differing effects of two intra- venous solutions on changes in intraoperative body temperature among patients undergoing graft replacement for abdominal aortic aneur- ysm. The study investigates the effects on changes in body temperature of major invasive surgery and the effectiveness of starting intra- venous infusion following induction of anesthe-
si a.
Materials and methods
The protocol our local ethics provided with
of this study was approved by committee. All patients were a full explanation about this
Received March 31, 2009 ; Accepted September 3, 2009
prospective study during consultation prior to surgery, and written informed consent was obtained from each patient.
This study was conducted with twenty patients who underwent scheduled surgery for graft replacement for abdominal aortic aneurysm between December, 2004 and January, 2007. The twenty patients were divided into two groups of ten. The first group was given a 10% amino acid solution (AmiparenTM : Group A), while the remaining ten were administered 5% acetated Ringer's solution with 5% glucose (Veen DTM : Group V). Thiamylal and vecuronium bromide were used to induce anesthesia, maintained epidurally by administration between Th12/L2, combined with a general anesthetic (air-oxygen- sevoflurane). Following anesthesia induction, a two-lumen central venous catheter was introduced into the internal jugular vein via which Group A was given 300 ml AmiparenTM and Group V was given 500 ml Veen DTM central venous line infusion over two hours, following each solution was given by continuous infusion of 60 ml/h. An extracellular solution (Veen FTM) and blood plasma substitute (SalinhesTM) were administered peripherally. Bladder temper- ature was used to gauge body temperature, which was measured prior to surgery and then at 15- minute intervals starting from 15 minutes after the start of infusion. Blood glucose levels were also measured prior to surgery and then at 60- minute intervals, starting 60 minutes after the start of the infusion. During surgery, only salvaged blood warmed with a warmer was used for blood infusions, no device (warm air or water) was used to maintain body temperature, and subjects were observed for shivering after decannulation.
Values are expressed as the mean ± SD, and analysis of variance and Student's t-test was
conducted, with P<0.05 considered
Results
significant.
Patient characteristics are shown in Table 1.
No significant differences were observed between groups by Student's t- test ; however, there were no significant differences between the groups in terms of combined fluid transfusion and blood transfusion volumes.
The body temperature (°C) of Group A sub- jects was 36.2±0.4 prior to surgery, and although it tended to drop between 15 and 90 minutes
after the start of infusion, reaching a minimum of 35.6+0.6, the fall was not significant. After 135 minutes, body temperature rose steadily, recover-
ing to almost preoperative levels at the 300- minute mark (Fig. 1). In Group V, the preoper-
ative body temperature which was 36.3±0.2 had significantly fallen between 60 and 225 minutes after infusion began, reaching a minimum of 35.
3±0.6. Body temperature subsequently rose somewhat, but did not recover to preoperative levels (Fig. 2).
(°C) 37-I
36
35
34-4 0 Fig. 1
60 120 180 240 300 (min)
Changes in the body temperature of Group A.
No significant differences were observed intraoper- ati vel y.
Time 0 : the time of starting infusion
Table 1 Patient characteristics and intraoperative data.
Group A (n-10) Group D (n10)
Age (years) Height (cm) Weight (kg)
Duration of operation (min) Duration of anesthesia (min) Volume of fluid transfusion (m1) Volume of blood transfusion (ml) Amount of bleeding (g)
Urinary volume (m1)
71.1+10.0 162.1+7.0 60.8± 11.3
213+42 328+59 3397+632
590+405 652 + 371 800+ 534
69.3+9.3 164.0+ 8.2 62.8+12.4
247+77 358+81 3634+931
677+446 887+589 654+ 357
(°C) 37-I
36
35
34 0 Fig. 2
II
VIII
60 120 180 240 300 (min)
Changes in the body temperature of Group V.
The body temperature was significantly lower between 60 and 225 minutes compared with the preoperative body temperature.
Time 0 : the time of starting infusion X : P<0.05 vs time 0
The change in blood glucose levels at 60 and 120 minutes were significantly elevated in Group A throughout surgery (Fig. 3), but levels were
significantly elevated in Group V during surgery (Fig. 4).
No shivering was observed in any Group A subject following decannulation, while two out of the ten Group V subjects exhibited whole body shivering.
Patients were transferred to the intensive care unit (ICU) following surgery. No change in general condition was observed in any patient while in ICU, and all patients were moved to a general ward the following day. The object patients all discharged from the hospital without hindrance, and were no death matters while
hospitalization.
Discussion (mg/dL)
300
200
100
0
Amiparen..300mL —)
Fig. 3
(mg/dL) 300
200
100
0
0 60 120 180 240 300 (min)
Changes in blood glucose levels of Group A.
The blood glucose level was significantly higher at 60 and 120 minutes compared with before infusion.
Time 0 : the time of starting infusion : P <0.05 vs time 0
' Veen DTM 500mL —
Fig. 4
0 60 120 180 240 (min)
Changes in blood glucose levels of Group V.
The blood glucose level was significantly higher intraoperatively compared with before infusion.
Time 0: the time of starting infusion X : P<0.05 vs time 0
It is known that when surgical patients are given a general anesthetic, body temperature falls in three phases, starting from the induction of anesthesia.' While under general anesthesic, the body's ability to regulate temperature is com- promised, heat is re-distributed between different areas of the body, and the temperature of the vital organs falls (core hypothermia resulting from redistribution of body heat).2'3 In addition, the fact that the patient is unclothed combined with surgical stress and the operative method (open abdominal surgery etc.) means an imbal- ance is created between the body's generation and diffusion of heat, further lowering body temperature. Without appropriate warming or retention of heat, the body is subject to hypother- mia upon waking. Hypothermia is particularly marked when surgery is prolonged or the opera- tive field is large, such as with surgery for
abdominal aortic aneurysm, when use of warm air or water is vital to prevent hypothermia.
Mild hypothermia following surgery can cause shivering and increase oxygen consumption,4"5 while more severe hypothermia may prolong the effects of muscle relaxants,6 delay postoperative
arousal,' aggravate blood loss,8 prolong bleeding time and PT and APTT9"10 and increase the likelihood of surgical site infection." Not only is shivering extremely unpleasant for the patient,
aggravating pain at the surgical site, it also raises
the rate of myocardial ischemia due to increased
oxygen consumption resulting from muscle con-
tractions.12 In view of the range of negative
implications for patients, it is recognized that intraoperative hypothermia should be checked, the patient's body should be physically warmed and kept warm, and that solutions and blood given intravenously to patients should be war- med ; however, in reality, factors such as a lack of medical equipment mean that in the clinical setting, such practices are not fully implemented.
Meanwhile, it has been reported that infusion with amino acid solution during the perioper- ative period curbs hypothermia.l3-16 Details such as the dosage, administration rate and period over which it should be administered have not been investigated, but there have been reports on the effectiveness both of preoperative administration13,14 and administration starting preoperatively and continuing during sur- gery.15,16 It is therefore possible that giving amino acid infusions under a range of different conditions could lead to the development of specific regimes for use in the clinical setting. As one such method, in this study we examined the effects of giving a rapid infusion of amino acid solution after induction of anesthesia on prevent- ing intraoperative hypothermia. When we compared the results with those for rapid infu- sion of acetated Ringer's solution with glucose, it became evident that rapid infusion with a gen- eral amino acid solution was effective in prevent- ing both intraoperative hypothermia and pos- toperative shivering, and it was confirmed that the administration of amino acids can be expect- ed to take effect comparatively quickly, even when administered after the induction of anes- thesia. In other words, even with a surgical patient undergoing highly invasive surgery, in which pre-surgical administration of amino acid infusion in the clinical setting is difficult, admin- istration of such an infusion after the induction of anesthesia allows for body temperature to be sufficiently managed to ensure that low body temperature does not develop.
The mechanism by which the administration of amino acids counters the onset of hypother- mia is unclear, but it has been reported that because administering amino acids increases oxygen uptake by the lungs and oxygen con- sumption by the inner organs, amino acids there- fore boost metabolism in peripheral tissue, thus promoting heat production,'7 suggesting that heat generation resulting from the administra- tion of amino acids occurs in tissue outside of the internal organs.18 Also, the increase in
energy consumption from administration of amino acids is dosage dependent, correlating with the speed at which protein is synthesized,"
and a blend of amino acids boosts muscle pro- tein synthesis, promoting storage of heat within the body.20 We can therefore surmise that the
synthesis of protein in the muscles brought about by administering amino acids causes heat to be produced.
Furthermore, while blood glucose levels of Group A rose significantly at 60 and 120 min- utes, but after 180 minutes fell back to around preoperative levels, no significant change was
observed throughout the procedure, while the blood glucose levels of Group V rose significant- ly from preoperative levels, and fell little after
surgery. It therefore appears that very little of the amino acid solution administered was used for gluconeogenesis ; rather, the process appear- ed to promote the consumption of glucose. This
suggests that heat generated from glucose did not contribute to maintaining or raising body tem- perature. In addition, because high postoper-
ative glucose levels increase the death rate among seriously ill patients following surgery,21 admin- istration of amino acid solution is more useful than acetated Ringer's solution with glucose.
However, there were no cases of the use of insu- lin since all patients' blood glucose level was under 230 while kept in ICU.
In conclusion, in open abdominal surgery, which is highly invasive and prolonged, amino acid solution infusions were able to maintain intraoperative body temperature without the use
of other equipment for this purpose. This study indicated that because administration of amino acids leads to heat generation, amino acid solu- tion infusion following induction of anesthesia is useful in preventing intraoperative hypother- mia and post-operative shivering.
References
1. Sessler DI (2005) Miller's Anesthesia 6th ed., In : Miller RD (ed) : Temperature monitoring, New York, NY, Churchill Livingstone, pp 1571-1597
2. Matsukawa T, Sessler DI, Sessler AM, Schroeder M, Ozaki M, Kurz A, Cheng C (1995) Heat flow and distribution during induction of general anesthesia.
Anesthesiology 82 : 662-673
3. Matsukawa T, Sessler DI, Christensen R, Ozaki M, Schroeder M (1995) Heat flow and distribution during epidural anesthesia. Anesthesiology 83 : 961-967 4. Bay J, Nunn JF, Prys-Roberts C (1968) Factors
influencing arterial P02 during recovery from anaesthe- sia. Br J Anaesth 40 : 398-407
5. Frank SM, Fleisher LA, Olson KF, Gorman RB, Higgins MS, Breslow MJ, Sitzmann JV, Beattie C (1995) Multivariate determinants of early postoperative oxygen consumption in elderly patients. Anesth- esiology 83 : 241-249
6. Heier T, Caldwell JE, Sessler DI, Miller RD (1991) Mild intraoperative hypothermia increases duration of action and spontaneous recovery of vecuronium block- ade during nitrous oxide-isoflurane anesthesia in humans. Anesthesiology 74 : 815-819
7. Lenhardt R, Marker E, Goll V, Tschernich H, Kurz A, Sessler DI, Narzt E, Lackner F (1997) Mild intraoperative hypothermia prolongs postanesthetic recovery. Anesthesiology 87 : 1318-1323
8. Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A (1996) Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty.
Lancet 347 : 289-292
9. Michelson AD, MacGregor H, Barnard MR, Kestin AS, Rohrer MJ, Valeri CR (1994) Reversible inhibition of human platelet activation by hypothermia in vivo and in vitro. Thromb Haemost 71 : 633-640
10. Rohrer MJ, Natale AM (1992) Effect of hypothermia on the coagulation cascade. Cri Care Med 20 : 1402- 1405
11. Kurz A, Sessler DI, Lenhardt R (1996) Perioperative normothermia to reduce the incidence of surgical wound infection and shorten hospitalization. Study of wound infection and temperature group. N Engl J Med 334: 1209-1215
12. Frank SM, Fleisher LA, Breslow MJ, Higgins MS, Olson KF, Kelly S, Beattie C (1997) Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial.
JAMA 277: 1127-1134
13. Sellden E, Brundin T, Wahren J (1994) Augmented thermic effect of amino acids under general anaesthe- sia : a mechanism useful for prevention of anaesthesia- induced hypothermia. Clin Sci 86 : 611-618 14. Sellden E, Branstrom R, Brundin T (1996) Preoper-
ative infusion of amino acids prevents postoperative hypothermia. Br J Anaesth 76 : 227-234
15. Sellden E, Lindahl SGE (1998) Postoperative nitro- gen excretion after amino acid-induced thermogenesis under anesthesia. Anesth Analg 87 : 641-646 16. Sellden E, Lindahl SGE (1999) Amino acid-induced
thermogenesis reduces hypothermia during anesthesia and shortens hospital stay. Anesth Analg 89: 1551- 1556
17. Brundin T, Wahren J (1994) Effects of i.v. amino acids on human splanchnic and whole body oxygen consumption, blood flow, and blood temperatures.
Am J Physiol 266 : E396-E402
18. Sellden E, Branstrom R, Brundin T (1996) Augment- ed thermic effect of amino acids under general anaesthe- sia occurs predominantly in extra-splanchnic tissues.
Clin Sci 91 : 431-439
19. Giordano M, Castellino P (1997) Correlation between amino acid induced changes in energy expend- iture and protein metabolism in humans. Nutrition 13 : 309-312
20. Yamaoka I, Doi M, Nakayama M, Ozeki A, Moch- izuki S, Sugahara K, Yoshizawa F (2006) Intravenous administration of amino acids during anesthesia stimu- lates muscle protein synthesis and heat accumulation in the body. Am J Physiol Endocrinol Metab 290 : E882 -E888
21. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345 : 1359-1367