phenylephrine and norepinephrine pretreatment for...
TRANSCRIPT
경희의학 : 제 32 권 제1 호 □ 증 례 □
J Kyung Hee Univ Med Cent : Vol. 32, No. 1, 2017
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Phenylephrine and Norepinephrine Pretreatment for Preventing
Postreperfusion Syndrome during a Pediatric Multivisceral
Organ Transplantation: A Case Report
Min Suk Chae, Nuri Lee, Da Hye Park, Jisoo Lee, Hyun Sik Jung,
Chul Soo Park, Jaemin Lee, Jong Ho Choi, Sang Hyun Hong
Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine,
The Catholic University of Korea, Seoul, Korea
Corresponding author: Sang Hyun Hong, Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222,
Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: +82-2-2258-6157, Fax: +82-2-537-1951E-mail: [email protected]
INTRODUCTION
Intestinal transplantation (ITx) is considered the final
treatment option for children with intestinal failure that
cannot absorb sufficient caloric requirements enterally
with resultant growth failure.(1) The primary diseases
causing intestinal failure in children consist of extended
total aganglionosis, gastrointestinal pseudo-obstruction,
and necrotizing enterocolitis.(2) ITx can be performed
in isolation or in combination with other organs, inclu-
ding the liver, pancreas, or spleen. The morbidity and
mortality of ITx have improved since the first report in
1960,(3) with a current estimated 1-year survival rate
of 73%.(2) These improvements resulted from advances
in immunosuppression, particularly following the
introduction of tacrolimus in 1990,(4) and perioperative
management of anesthesia and surgery.(5)
Postreperfusion syndrome (PRS) is frequently seen in
solid organ transplantation, and is associated with poor
outcome of the graft or recipient.(6) In liver trans-
plantation, PRS is defined as a ≥ 30% decrease in
mean arterial pressure (MAP) within 5 minutes after
graft reperfusion and continuing for at least 1 minute.(7)
Significant PRS includes prolonged or recurrent
fibrinolysis requiring administration of antifibrinolytic
agents.(8) It has been reported that PRS can be
ameliorated by pretreatment with vasopressors before
graft reperfusion in liver transplantation.(9) Severe
hemodynamic fluctuation with acidbase or electrolyte
imbalance was seen during graft reperfusion in small
bowel transplantation.(10) However, there have been
insufficient studies of methods for prevention of PRS
in case of pediatric multivisceral organ transplantation.
In the present case, we performed strong vasopressor
pretreatment to prevent severe hypotension during graft
reperfusion, and ensure rapid recovery from hemo-
dynamic and metabolic disturbance after graft reper-
fusion in pediatric multivisceral organ transplantation.
− Min Suk Chae, et al：Pretreatment and Postreperfusion Syndrome −
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Fig. 1. Preoperative abdominal X-ray findings.
CASE REPORT
A 30-month-old toddler (male; blood type, A+;
height, 90.1 cm; weight, 13.5 kg) with chronic intes-
tinal pseudo-obstruction was scheduled for multivisceral
organ transplantation. He was born at 36 weeks of
gestation and weighed 2.99 kg with normal delivery. In
antepartum care using sonography, he showed dis-
tention of the bladder, and thus underwent a procedure
to reduce bladder distension at a local obstetric clinic.
After birth, there were no abnormal physical findings.
At 70 days after birth, he suddenly presented with
nausea, vomiting, and abdominal distension. Multi-
disciplinary examinations and exploratory surgery with
colostomy were performed at a local pediatric clinic,
but a proper diagnosis was not made. After thorough
examination at a tertiary center, he was diagnosed with
intestinal pseudo-obstruction due to visceral myopathy
and repeatedly treated with total parenteral nutrition
(TPN) for several years. However, his symptoms did
not improve, and he was finally transferred to our
center for ITx.
We planned to perform multivisceral organ trans-
plantation, including of the stomach, duodenum, pancreas,
spleen, jejunum, ileum, and colon, excluding the
rectum. The patient showed stable preoperative hemo-
dynamics without any vasopressor infusion, and labo-
ratory parameters, including hemoglobin (11.5 g/dL),
sodium (141 mmol/L), potassium (4.5 mmol/L),
calcium (9.0 mmol/L), phosphorus (5.6 mmol/L),
magnesium (2.0 mmol/L), creatinine (0.32 mg/dL), total
bilirubin (0.26 mg/dL), γ-glutamyl transpeptidase (12
units/L), alkaline phosphatase (164 units/L), aspartate
transaminase (AST; 26 units/L), alanine transaminase
(ALT; 17 units/L), international normalized ratio (INR;
1.19), platelet count (152 × 103/µL), albumin (3.5
g/dL), and leukocyte count (4.29 × 109/L) were within
the normal ranges. Electrocardiography showed normal
sinus rhythm. Features of bowel distension and ileus on
preoperative abdominal X-ray examination are presented
in Figure 1. The recipient received visceral organs
from a deceased 4-year-old donor (male; blood type,
A+; height, 103 cm; weight, 24.5 kg) with brain death
caused by a traffic accident.
The recipient was sedated using intravenous ketamine
(0.5 mg/kg) with glycopyrrolate (0.004 mg/kg) under
meticulous monitoring in the waiting room, and then
transferred into the operating room (OR). The
recipient’s vital signs were measured immediately
before induction of anesthesia and were as follows:
blood pressure, 115/71 (86) mmHg; heart rate (HR),
113 beats/min; body temperature (BT), 36.5°C; and
oxygen saturation, 100% on pulse oximetry. Anesthesia
was induced using intravenous propofol (1.0 mg/kg)
and rocuronium (0.8 mg/kg). After orotracheal intu-
bation, anesthesia was maintained by inhalation of
sevoflurane (end-tidal minimum alveolar concentration,
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0.51.0 vol%) and intermittent injection of fentanyl (0.5
μg/kg). The right radial artery was cannulated after the
modified Allen’s test for continuous arterial blood
pressure monitoring, and a central venous catheter was
placed in the right subclavian vein for drug admini-
stration and central venous pressure (CVP) monitoring.
In surgery, the aorta and inferior vena cava (IVC) of
the recipient were manipulated for end-to-side anasto-
mosis of graft vessels, including the hepatic artery, left
gastric artery, splenic artery, superior mesenteric artery
(SMA), and portal vein. Graft arteries were anasto-
mosed with the infrarenal aorta of the recipient using
arterial bridge grafts, including the celiac trunk and
SMA. Graft venous drainage was performed with
anastomosis between the graft portal vein and infra-
renal IVC of the recipient. The gastrointestinal tract
was reconstructed with end-to-end anastomosis of the
proximal site of the graft, including gastrogastrostomy
with pyloroplasty, jejunojejunostomy, and Roux-en-Y
choledochojejunostomy. Santuli-type ileostomy was
conducted 20 cm proximal to the ileocecal valve with
easy drainage. The operation duration was about 17
hours, and the total ischemic time was 404 minutes.
The multivisceral organs were preserved using a
histidinetryptophanketoglutarate solution (CustodiolⓇ
;
Dr. Franz Köhler Chemie, Bensheim, Germany). Gross
findings of the grafts were checked on a back-table in
the OR, and no significant abnormalities were detected.
After clamping of major vessels, including the infra-
renal aorta and IVC of the recipient, administration of
a low dose of intravenous norepinephrine (0.05 μg/kg/min)
was begun to maintain appropriate perfusion pressure.
At 5 minutes before multivisceral graft reperfusion, the
vital signs and arterial blood gas analysis (ABGA)
results of the recipient were as follows: mean arterial
blood pressure, 62 mmHg; HR, 112 beats/min; CVP, 4
mmHg; BT 36.8°C; pH, 7.319; base excess, 6.2;
hemoglobin, 8.4 g/dL; PaO2, 242 mmHg; SaO2, 99.8%,
and PaCO2, 37.6 mmHg. Immediately before multi-
visceral graft reperfusion, the recipient was pretreated
with an intravenous bolus of phenylephrine (2.0 μg/kg)
with increasing norepinephrine infusion (0.1 μg/kg/min)
to prevent the development of severe PRS. After multi-
visceral graft reperfusion, the mean arterial blood
pressure decreased to a nadir of 41 mmHg, but
promptly increased to 60 mmHg within 1 minute.
Changes in HR and CVP were 112 to 115 beats/min
and 4 to 6 mmHg, respectively. In ABGA findings, the
degree of arterial acidosis, such as pH and base excess,
showed little change between 5 minutes before and
after multivisceral graft reperfusion, and improved
gradually until 1 hour after multivisceral graft reper-
fusion. The serum lactate level increased from 1.1
mg/dL at induction of anesthesia to 6.0 mg/dL at 5
minutes before graft reperfusion, and decreased to 3.3
mg/dL at the end of surgery. There were few dynamic
changes in coagulation parameters between 1 hour
before and after multivisceral organ reperfusion: INR,
3.57 vs. 2.85; activated prothrombin time, 120 vs. 120
s; fibrinogen, 42 vs. 92 mg/dL; antithrombin III, 15.5
vs. 19.4%; D-dimer, 2.18 vs 2.2 mg/L; fibrinogen
degradation products, 7.4 vs. 6.7 μg/mL, and platelet
count 53 vs 30 (×103/μL). Severe oozing in the surgical
field was not presented. Based on the recipient’s
condition, intravenous norepinephrine infusion was
tapered to 0.01 μg/kg/min at 1 hour after multivisceral
graft reperfusion, and finally discontinued at the end of
surgery. The intraoperative changes in vital signs,
ABGA findings, and vasopressor dosages are shown in
Table 1.
During the whole surgery, the amounts of blood
products transfused were as follows: four units of
packed red blood cells; one unit of frozen fresh
plasma; one unit of single donor platelets, and two
units of cryoprecipitate. Total amounts of crystalloid
and colloid, diluted with albumin 25% to 12.5%, were
− Min Suk Chae, et al：Pretreatment and Postreperfusion Syndrome −
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Table 1. 다장기 이식 수술 보인 활력 징후, 동맥 가스 승압제에 한 표
I I+1h I+2h I+3h I+4h R-5min R R+1min R+2min R+3min R+4min R+5min R+30min R+1h R+2h R+3h End
Vital signs
SAP (mmHg) 115 79 97 85 85 85 52 90 90 88 87 88 90 91 92 95 95
DAP (mmHg) 71 53 65 52 53 51 36 45 48 49 48 47 48 49 48 63 65
MAP (mmHg) 86 62 76 63 64 62 41 60 62 62 61 61 62 63 63 74 75
HR (beats/min) 113 121 117 126 126 112 115 100 105 110 130 136 136 132 135 129 129
CVP (mmHg) 5 4 6 5 6
BT (°C) 36.5 36.8 35 35.2 36.0 36.2
Arterial blood gas analysis
pH 7.33 7.33 7.30 7.35 7.33 7.31 7.34 7.44 7.40 7.43 7.40 7.46
Base excess -7.5 -7.6 -9.5 -7.8 -6.9 -6.2 -5.6 -0.7 -0.2 0.6 -2.4 0.5
Lactate (mg/dL) 1.1 2.4 2.7 3.0 4.1 6.0 5.8 5.0 4.5 3.6 3.5 3.3
Hemoglobin
(g/dL)
10.5 8.9 8.6 8.9 8 8.4 10.2 8 8.7 11.8 12.2 9.8
PaO2 (mmHg) 195 500 327 257 238 242 250 246 232 204 152 143
SaO2 (%) 98.8 99.6 99.5 97.6 97.8 99.8 99.8 100 99.9 98.4 99.4 99.2
PaCO2 (mmHg) 33.3 33.2 32.5 30 34.1 37.6 35.4 33.5 38.7 36.6 35.2 33.1
Vasopressor administration
Norepinephrine
(μg/kg/min)
0.05 1.0 0.05 0.01 none
Phenylephrine
(μg)
27
Abbreviations: I, anesthetic induction; R, multi-visceral grafts reperfusion; SAP, systolic arterial pressure; DAP, diastolic arterial pressure; MAP, mean arterial
pressure; HR, heart rate; CVP, central venous pressure; BT, body temperature.
4,900 mL and 150 mL, respectively. Estimated blood
loss was 1,300 mL. Urine output was 3.31 mL/kg/h.
Total doses of bicarbonate, calcium chloride, and insulin
were 55 mEq, 420 mg, and two units, respectively.
Postoperatively, the recipient was sent to the
intensive care unit (ICU) in the intubated state and
maintained with mechanical ventilator support. The
arterial blood pressure was within the normal range
without vasopressor infusion, but post-transplant chest
X-ray showed haziness on both lung fields. After
adjustment of fluid balance with antibiotic coverage,
the chest X-ray findings improved gradually and the
recipient was weaned from the mechanical ventilator on
postoperative day (POD) 10. Feeding was begun by
gastrostomy tube and the graft condition was evaluated
regularly by endoscopy during the ICU stay. Immuno-
suppression was induced with a combination of basili-
ximab and rabbit anti-thymocyte globulin, and main-
tained with tacrolimus monotherapy. Steroid was
tapered during the early postoperative period. The
recipient underwent conservative management under
meticulous monitoring, and was transferred to a ward
in tolerable condition on POD 11. The recipient was
discharged in a satisfactory condition 6 months after
multivisceral organ transplantation.
DISCUSSION
The main finding of our case was that pretreatment
with an intravenous bolus of phenylephrine (2.0 μg/kg)
and norepinephrine infusion (1.0 μg/kg/min) imme-
diately before graft reperfusion reduced the severity of
PRS during pediatric multivisceral organ transplan-
tation. Little change in arterial pH or base excess was
− 경희의학 제32 권 제1 호 2017 −
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observed before vs. after graft reperfusion. To our
knowledge, this is the first description of a positive
effect of pretreatment on hemodynamic and metabolic
homeostasis during graft reperfusion in pediatric
multivisceral transplantation.
PRS is frequently seen in solid organ transplantation,
but the underlying mechanism is complex.(11) In adult
ITx, the incidence of PRS is about 50% and is
associated with postoperative kidney injury and early
mortality. Total cold ischemic time and preoperative
glomerular filtration rate were considered to be inde-
pendent predictors of PRS.(12) Hemodynamic instability,
arterial acidosis, and hypocoagulation occur after graft
reperfusion during adult ITx. These signs indicate graft
dysfunction and poor postoperative outcome.(13)
Ischemiareperfusion injury to the intestinal graft may
cause metabolic abnormalities after graft reper-
fusion.(14) In our case, the changes in pH and base
excess improved immediately after graft reperfusion,
and hemostatic parameters and bleeding tendency in the
surgical field were not aggravated.
Many groups have investigated ways of attenuating
the development of PRS, because it is known to have
a negative effect on the postoperative outcome of the
recipient or graft. In adult liver transplantation, pre-
treatment with epinephrine and phenylephrine were
effective to prevent PRS, with no immediate or delayed
negative effects. The total intraoperative requirement
for vasopressors, such as epinephrine and dopamine,
was significantly reduced in the pretreatment group.
The doses of epinephrine and phenylephrine were
chosen empirically.[9] In our case, MAP declined from
62 mmHg before graft reperfusion to 41 mmHg
immediately after graft reperfusion (34% decrease), but
was restored to the level prior to graft reperfusion
within 1 minute. Rapid recovery of hemodynamic
instability during graft reperfusion may attenuate to the
development of graft injury and contribute to
circulatory homeostasis of multivisceral grafts.
There have been few reports to date regarding the
effects of strong vasopressor pretreatment on hemo-
dynamic and metabolic outcomes of graft reperfusion
in pediatric multivisceral organ transplantation. One
case reported by Park et al.(15) suggested that
prolonged hypotension with severe metabolic acidosis
and hypothermia developed after graft reperfusion,
although intravenous epinephrine was administered
many times after graft reperfusion during a case of
pediatric multivisceral organ transplantation, including
of the liver, spleen, stomach, duodenum, small bowel,
colon, and pancreas. Eventually, the recipient showed
liver graft failure and underwent isolated liver
re-transplantation on POD 3. In our case, timely
administration of vasopressors before graft reperfusion
may have aided the recovery of hemodynamic and
metabolic stability after graft reperfusion.
In conclusion, pretreatment with strong vasopressors
immediately before graft reperfusion during pediatric
multivisceral organ transplantation should be consi-
dered, as the large size of an en bloc graft could cause
severe and prolonged PRS, which may have negative
effects on graft and patient outcomes.
ABSTRACT
Phenylephrine and Norepinephrine
Pretreatment for Preventing
Postreperfusion Syndrome during a
Pediatric Multivisceral Organ
Transplantation: A Case Report
Min Suk Chae, Nuri Lee, Da Hye Park, Jisoo Lee,
Hyun Sik Jung, Chul Soo Park, Jaemin Lee,
Jong Ho Choi, Sang Hyun Hong
Department of Anesthesiology and Pain Medicine, Seoul St.
Mary’s Hospital, College of Medicine, The Catholic University
of Korea, Seoul, Republic of Korea
− Min Suk Chae, et al：Pretreatment and Postreperfusion Syndrome −
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Multivisceral organ transplantation is the final treat-
ment option for children that have difficulty in
absorbing sufficient enteral nutrition. Postreperfusion
syndrome (PRS) is frequently seen in solid organ
transplantation, and has a negative effect on graft
and/or recipient outcome. Here, we describe a 30-
month-old male toddler with chronic intestinal pseudo-
obstruction treated with multivisceral organ transplan-
tation, including of the stomach, duodenum, pancreas,
spleen, jejunum, ileum, and colon, but not the rectum.
Immediately before multivisceral graft reperfusion, the
recipient was pretreated with an intravenous bolus of
phenylephrine (2.0 μg/kg) with increasing norepine-
phrine infusion. Pretreatment with phenylephrine and
norepinephrine to prevent PRS reduced the severity and
duration of severe hypotension and metabolic distur-
bance after graft reperfusion. As prolonged severe
hypotension during graft reperfusion is associated with
adverse outcomes, timely pretreatment with vaso-
pressors before graft reperfusion is required to attenuate
the development of severe PRS in pediatric multi-
visceral organ transplantation.
Abbreviations: ITx, intestinal transplantation; PRS,
postreperfusion syndrome; TPN, total partenteral
nutrition; ICU, intensive care unit; INR, international
normalized ratio.
Key Words: Transplantation, Intestines, Reperfusion
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