Changes in core temperature during graft warm ischemia and reperfusion phases during living donor liver transplant: Adult versus pediatric

Changes  in core temperature during graft warm ischemia and reperfusion phases during living donor liver transplant: Adult versus pediatric

Ibrahim Abdelkader Salama,a MD; Mohamed Hussein Abdullah,b MD;

Wesam Saber Morad,c MD

a) Department of Hepatobilliary Surgery, Menophyia University, Shebin Elkom, Egypt.

b) Department of Anesthesia, Menophyia University, Shebin Elkom, Egypt.

c) Department of Public Health National Liver Institute, Menophyia University, Shebin Elkom, Egypt.

Abstract

Background: Maintaining normothermia is essential during liver transplant. Serious adverse outcomes from perioperative hypothermia are well documented.

Objective: To evaluate the core temperature changes during graft warm ischemia and reperfusion periods in adult and pediatric cases.

Method: 30  recipients,(adult n=15  and  pediatric n=15)  were  enrolled  in this  study.

Nasopharyngeal core temperature (NC'I) was recorded at the following points: 5 and 30 minutes after induction of anesthesia (tempi&2), the lowest NCT during dissection phase (temp3), the lowest NCT during the anhepatic phase and before implantation  of the graft (temp4), lowest NCT during warm  ischemia  (putting  the graft  at its bed till reperfusion)  (temp5),  also at 5 (temp6)  and 30 minutes  (temp7) after reperfusion, then before the end of surgery  (temp8).

Results: Significant decrease in core temperature during the anhepatic phase (temp4), warm ischemia time (temp5), 5 minutes  after reperfusion  (temp6) and 30 minutes  after reperfusion (temp7)  with  mean  values  of  36.4  ± 0.47°C,  35.4±0.45°C, 35.2±0.50°C and  35.2±0.52°C respectively in the pediatric group, while in adult group the mean values36.3±0.330C, 36.1±0.380C,

36.1±0.6JOC and 35.9±0.34°C respectively.

Conclusion:  Significant drop in NCT was observed at the beginning  of the warm ischemia period  that persisted  through  the reperfusion phase in both  adult and pediatric  recipients. Children  with a body  weight  <14 kg had their core temperatures affected  more  than adult patients  because  of   receiving  relatively  large  grafts  with   a  greater  GRWR.

Key words: Hypothermia, ischemia reperfusion, living liver transplant.

Introduction:

Hypothermia  is an important  and frequent problem during liver transplant. I Prospective; randomized trials have shown that even mild hypothermia causes numerous adverse outcomes in a variety of patient populations. Hypothermia-induced complications  include morbid myocardial outcomes2 secondary  to sympathetic nervous system activation,3 surgical wound  infection,4 coagulopathy5 increased  allergenic  transfusions,6 negative nitrogen  balance,7 delayed  wound  healing,8 delayed post  anesthetic recovery period,9

prolonged  hospitalization,8 shivering,10 and patient discomfort.ll The  core   thermal compartment is composed of highly perfused tissues  whose  temperature is uniform  and higher  when  compared  with  the rest  of the body.  Temperature  in this compartment can be traced either in the pulmonary artery, distal esophagus, tympanic membrane or nasopharynx.l2,13

Liver transplant (LT) is considered to be an ultra major  surgery,   hypothermia  during LT is multi factorial and results from massive fluid administration, convective and evaporative

losses from prolonged exposure of viscera, diminished hepatic  energy  production, and implantation  of a cold graft of large  thermal mass.14 The liver  graft  volume  to recipient body weight ratio (GRWR)  of at least 1.0 is required to prevent liver dysfunction after liver transplantation.ts Therefore, left  lateral segmentectomy or lobectomy and right hepatectomy are performed for LDLT  in pediatric  and adult  recipients  respectively.

Aim of the work:

To study core temperature changes during graft warm ischemia  and reperfusion  phases in adult and pediatric recipients.

Patients and methods:

This study was carried out after approval from the local ethical transplant committee in the  National Liver  Institute - Menophyia University and informed consents from the patients (from parents in pediatric cases). Our living  liver transplant  program  was initiated on Apri12003. Thirty recipients were enrolled in this study from December 2008 to December

2010 and were divided equally into two groups (adult and pediatric).  All donors were related to their recipients and were carefully assessed and approved by transplantation ethical committees.

Adequate preoxygenation was done before the administration of any pharmacological agents.  In the adult  group  (n=15),  induction was done  by fentanyl2J.Lg/kg,  propofol 2-3 mglkg. LV, while muscle relaxation was made by  I.V  rocuronium. In  the  pediatric group (n=15), intravenous access had been established previously in   12 cases either for   the pretransplant medications or for preoperative ICU management.  So, intravenous induction was preceded in them while the remaining  (3 children) were accomplished by sevoflurane inhalational induction. Atropine was given 10-

30J.Lg/kg.Fentanyl2J.Lg/.kg, sodium thiopental,

4-6  J.Lg/kg. I.V, in cases   of intravenous induction, while muscle relaxation was made by I.V rocuronium. Maintenance  of anesthesia in both groups was achieved using isoflurane,

and a mixture of air and oxygen (Fi02 0.4) in a low flow of one L/min.

Core   temperature was  monitored by nasopharyngeal probe using  (Cicero  EM• Drager Medical AG&Co-Germany).Operating room temperature  was set at 24°C the night before surgery.The heat conservation strategies and   the  warming devices included water mattress (hyper-hypothermic bad, seabrook, medical system Inc,  Cincinnati,  Ohio, USA) and forced air worming device (Bair Hugger, Arizant Health care Inc, USA) and both were set at 38°C from before induction tell the end of surgery, and  low  flow  anesthesia of lL/minute. Moreover, the  four   extremities were wrapped with cotton bandages, and then covered by stockinet A filter humidifier (Altec, Rusch Mirandola, Italy) was used to maintain the humidity  of anesthetic  gases. Fluids and blood  products  were warmed  and  transfused by using (Bair Hugger, Ranger, blood and fluid warming system, Arizant Health care Inc, USA), and fast flow fluid warmer (Ievell  ,H-

1200,  smith  medical  ASD  Inc,  Rockland,

USA). Head and extremity  wraps, to prevent intraoperative hypothermia. The goals of fluid management in all our recipients were  to maintain  normovolemia, adequate  oxygen• carrying capacity and homeostasis. Fluid given consisted  of  crystalloids (Ringer's  acetate), albumin 5% and blood products. The size of the obtained hepatic grafts were determined according  to recipient  size and preoperative radiological evaluation.l6,17 In the adult group, right  or extended right  hepatectomy was obtained, while left lateral hepatectomy  was enough for the pediatric cases.

The weight of the graft is obtained before implantation. Prior to engraftment, the donor graft was   removed and   prepared for implantation in a back table procedure.  The graft  was flushed and preserved in HTK solution (Custodio}, Bretschnieder HTK solution, Bensheim, Germany) and, if any vascular reconstruction was necessary, it was performed Figure(l).

Figure (1): Graft flushing and vascular reconstruction in back table prior to implant.

Recipient operations:

Left  lateral segment  I Left  lobe  (in pediatric group):

After hepatectomy with caval preservation, the graft was implanted in a piggyback fashion,

either to extended orifices of the right, middle, and left hepatic veins in children or to the orifices of the middle and left hepatic veins in adults.t8,19 A surgicalloupe was  used  for arterial anastomoses in most pediatric cases and biliary reconstructions were performed with a Raux-en-Y limb. Doppler ultrasound was performed before and after closure of the abdomen.

Right lobe (in adult group):

After hepatectomy with caval preservation, the graft was implanted also in a piggyback fashion. The opening of the left and middle

hepatic veins was oversewn. To ensure optimal graft outflow, the right hepatic vein orifice was enlarged by making a caudal extension onto the inferior vena cava. Donor portal vein was anastomosed to the recipienf s right or main portal vein. Arterial anastomoses were done using surgical Ioupe. Biliary reconstruction was individualized. Duct- to• duct anastomosis with stent when technically favorable was done. Most often, Roux-en-Y hepatica-jejunostomy was used. Multiple ducts near each other were reconstructed as a single duct anastomosis by suturing the opposing duct sidewalls together.In the event of multiple ducts with significant size discrepancy with the recipient common bile duct, a Roux-en-Y limb  was constructed for biliary  enteric drainage Figure(l).

Figure (2): Implantation of a right lobe in adult recipient.

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Measurements:

Nasopharyngeal core temperature (NCT)

was recorded at the following  points: 5, 30 minutes after  induction of   anesthesia (temp1&2), the lowest NCT during dissection phase (temp3),the lowest NCT during the anhepatic phase and before implantation of the graft (temp4), lowest NCT during warm ischemia (putting the graft at its bed till reperfusion) (tempS), also at 5 (temp6), and

30 minutes (temp7) after reperfusion,  then

before  the   end   of   surgery  (tempS).

Statistical analysis:

Student t-test was done for normally distributed quantitative variables to measure mean    and   standard  deviation  (SD).

P-value < 0.05 was considered significant.

Mann-Whitney test was done for quantitative variables which were not normally distributed and p-value < 0.05 was considered significant.

In each group, Paired t- test was done to compare NCT changes all through the surgical procedure. Spearman's correlation test was done to study correlation between one qualitative variable  and one quantitative variable or two quantitative variables of not normally distributed data and p- value less than   0.05   was  considered significant.

Results:

Thirty recipients were enrolled in this study. The indications of the transplantation in pediatrics were mainly for biliary atresia in 8 children, congenital hepatic fibrosis in 2, Byler's disease in 2, Budd-chiari syndrome in one child, hepatoblastoma in one child and Haemangioma in one child. In the adults the indications were mainly post HCV cirrhosis in9 patients, cryptogenic cirrhosis in2 patients, HCC in 2 patients and 2 patients with primary scleroses  cholangitis  (PSC)  Table(l).

Table (1): Indication of transplantation in pediatrics and adult patients.

HCC: Hepatocelluler carcinoma, ESLD: End stage liver disease, HCV: Hepatitis C virus, PSC: Primary scelerosing cholangitis

The left lateral segment (segment 2, 3) was used in15 pediatric recipients, while right lobe without middle hepatic vein (segment 4-8) was used in 14 adult recipients and left lobe (segment 1-4) was used in one adult recipient. Age, height, recipient weight, liver graft weight, cold ischemia time and anhepatic phase time were significantly greater in adult group. However  graft  recipient  weight  ratio  was

significantly greater  in  pediatric  group Table(2). The remaining liver volume in all donors was 35% of the calculated whole liver volume, and macro vesicular steatosis in all grafts was 10% (estimated by routine percutaneous liver biopsy inall donors).There were no complications related to any of the warming devices in any patient.

Table (2): Differences  between studied groups regarding recipient criteria, grafts and intraoperative events.

PELD score; pediatric end stage liver disease, MELD; model of end stage liver disease,, GRWR; graft  recipient  body  weight  ratio, CIT; cold  ischemia  time,  WIT;  warm  ischemia  time  and Anhepatic phase time.*Mann Whitney test

Changes  in NCT during the surgical procedure in both groups:

Thirty minutes after induction of anesthesia, mild  but  not  significant hypothermia was present inboth  groups, and NCT dropped from (temp 1)   37±0.28°C  to   reach  (temp2)

36.8±0.27°C  in the pediatric  group,  while in the  adult  group  it  dropped  from  (tempi)

36.9±0.43°C to reach  (temp2) 36.8±42°C. During the dissection phase (temp3) the mean NCT  in  pediatric and  adult   group were

36.4±0.30°C  and 36.7±0.44°C respectively.

However,both groups experienced a significant decrease in  core   temperature during the anhepatic phase (temp4), wann  ischemia time (temp5), 5 minutes after reperfusion  (temp6) and 30 minutes after reperfusion (temp?) with mean values of 36.4 ± 0.47°C, 35.4±0.45°C,

35.2±0.50°C and 35.2±0.52°C respectively in the pediatric  group, while in adult group  the mean  values 36.3±0.33°C, 36.1±0.38°C,

36.1±0.61°C and 35.9±0.34°C respectively

Figures(3,4).

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36

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35

34

Post          30mlnures   Olsuctlo·n     Anhe.patlt                 Ourhg           5 mlnpos t   30m     pose Endot ilduc:tion                         post                phas.e         phase                                          wonn      re:pe.ffuslon   reperfu.s-ion     surgery

temp            Induction                                                       ischemia

Figure (3): Changes in nasopharyngeal core temperature (NC1) in pediatric groups during phases of liver transplantation procedure.

Adult group

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Figure (4):Changesin nasopharyngeal core temperature (NCT) in adult groups during phases of liver transplantation procedure.

The decrease in NCT at the time of implantation which is the warm ischemia time (tempS) and 5 minutes after reperfusion phase

(temp6) was found to be correlated with GRWR only not the graft weight inthe pediatric group Table(3).

Table (3):The correlation of GRWR and graft weight at different phases of surgery.

Temp5: during warm ischemia,Temp 6:5min post reper.fosion, Temp 7: 30min post reperfusion, GRWR: graft recipient body weight ratio, *positive correlation with p < 0.05.

Discussion:

Core temperature is usually measured as an approximation   to hypothalamic  temperature. As hypothalamic temperature cannot  be measured directly, various sites have been used to give an approximation.20,21 Tympanic membrane temperature  is usually thought to give  a good  estimate, but  nasopharyngeal, esophageal and   bladder are   acceptable alternatives. The lower third of the esophagus may be unreliable in LT as the cold donor graft is placed in close proximity.

Generally, following induction of anesthesia there is an   internal core  to-peripheral redistribution of body heat that usually reduces core temperature  by 0.5 to 1.5°C in the first

30 minutes.22 However,  this post induction

decrease in core  temperature did occur  in recipients of the present study and this might be attributed to the adequate heat conservation methods used that minimized the surface temperature of the recipients so decreasing the effect of redistribution.  During the dissection phase, core temperatures decreased slightly in both groups, but decreased significantly during the warm ischemia  and reperfusion phases.

It is known that in non-liver transplantation

surgical procedures, normothermia usually can be maintained with   an operating room temperature of24°C to 26°C regardless of type and length of anesthesia or surgery.23,24 Since room   temperature is stabilized at 24°C, therefore, the sudden decrease in NCT in the anhepatic phase and especially the reperfusion phase must be inherent to the   liver transplantation procedure.

Inthe anhepatic phase, the native liver

(large

heat producer) is absent and those patients produce less heat. This is also, associated with increase heat losses.14 On the other hand, the donor graft, which has been preserved in 4°C HTK solution, is then placed in the abdominal cavity.  During  vascular  reconstruction, the graft is flushed with 4°C lactated Ringer's solution to wash the cold preservative solution from  the new  graft  before  reperfusion.  The cold donor graft and cold lactated Ringer's flush solution caused a significant decrease in core temperature in  both groups  during  the anhepatic phase but it was more significant in the pediatric age group  than  the adult  age

group. The  additional decrease in  core temperature  after reperfusion  was caused by the hypothermic blood coming from the hepatic veins to the circulation  after passing through the cold donor graft.25

Although the decrease in NCT in the anhepatic and reperfusion phases  must be related to the amount of the cold graft tissue (graft weight) and the recipient size. These 2 factors can be obtained by using  the graft recipient weight  ratio  (GRWR).  It is  well known  that  in pediatric living  donors  liver transplantation, the smallest functional unit of a graft should include the hepatic artery, portal vein, hepatic vein, and bile duct. So, a left• lateral liver graft should consist of at least segments  2 and 3. Which  although  small, it may still be large for a pediatric recipient, which may    affect core temperature significantly. Our results showed that the core temperature in pediatric  patients  with  body weight less than 14 Kg with a mean value of

9.66 (2.66) kg, and receiving a liver graft with a greater GRWR  2.84  (0.48), decreased significantly more than in adult recipients with mean body weight 82.86 (7.41) kg and GRWR

1.16 (0.14).

Efforts to maintain normothermia  or slight hyperthermia in the dissection phase are necessary to prevent severe hypothermia  with subsequent complications in the anhepatic and reperfusion   phases.26,27 Steib   A   and associates,28 evaluated  the  benefit of  an esophageal rewarmer, used   during liver transplantation surgery,  and they  concluded that  the esophageal heat exchanger   allowed better rewarming after revascularization of the graft, but  was unable to prevent cardiac hypothermia at unclamping.

Inconclusion, A sudden significant drop in NCT  was observed  at the  beginning  of  the warm ischemia period that persists through the reperfusion  phase in both adult and pediatric recipients.  Children  with a body  weight  less than 14 kg had their core temperatures affected more than adult patients because of receiving relatively large grafts with a greater GBWR. Several  heat conservation and preservation strategies  are  of great  importance to reduce such risk.Correlation with the other associated clinical conditions like  post  reperfusion

syndrome, graft survival and post operative ICU course  are points  of further future evaluation.

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