1、Antidiuretic Hormone ReleaseDuring Laparoscopic Donor NephrectomyEric J. Hazebroek, MD; Robert de Vos tot Nederveen Cappel, MD; Diederik Gommers, MD, PhD;Teun van Gelder, MD, PhD; Willem Weimar, MD, PhD; Ewout W. Steyerberg, PhD;H. Jaap Bonjer, MD, PhD; Jan N. M. IJzermans, MD, PhDBackground: During
2、 laparoscopic procedures, in-creased intra-abdominal pressure may cause transient re-nal dysfunction due to impaired renal blood flow and in-duction of neurohormones. However, the relationshipbetween antidiuretic hormone (ADH) secretion and in-creased intra-abdominal pressure is poorly understood.Hy
3、pothesis: Laparoscopic donor nephrectomy (LDN)is associated with an increase in plasma ADH concen-tration, which influences renal function in both the do-nor and transplanted graft.Objectives: To evaluate plasma ADH levels during LDNand to correlate ADH levels with graft function.Design and Interven
4、tions: In 30 patients who un-derwent LDN, plasma ADH levels were collected beforeinsufflation, during surgery, after desufflation, and 24hours after the procedure. In 6 patients who had opendonor nephrectomy, blood samples were obtained as con-trols. Furthermore, graft function, operative character-
5、istics, and clinical outcome were compared.Setting: University hospital.Results: In the LDN group, mean ADH levels duringpneumoperitoneum and 30 minutes postinsufflation weresignificantly higher compared with preinsufflation val-ues (PH11021.001). Twenty-four hours after LDN, mean ADHlevels had retu
6、rned to normal values. There were no sig-nificant differences in ADH levels in the open donor ne-phrectomy group. No significant differences in eitherintraoperative diuresis, blood pressure readings, or post-operative graft function were documented among the 2groups.Conclusions: In this study, LDN w
7、as associated with anincrease in plasma ADH that appeared to be related toincreased intra-abdominal pressure. We conclude that theincreased ADH concentrations during LDN are not as-sociated with clinically significant changes in either thekidney donor or the transplanted graft.Arch Surg. 2002;137:60
8、0-604LAPAROSCOPIC SURGERY re-quires the use of pneumo-peritoneum to create a work-ing space in the abdominalcavity for the safe introduc-tion of trocars and other instruments aswell as exposure of the abdominal con-tents. Intraperitoneal insufflation withcarbon dioxide is the most commonly usedmetho
9、d to elevate the abdominal walland suppress the viscera. Clinical andexperimental studies have shown that in-creased intra-abdominal pressure is asso-ciated with transient renal dysfunction(oliguria) due to impaired renal blood flow,as a consequence of compression of the re-nal parenchyma and renal
10、vessels as wellas increased systemic resistance.1-3In ad-dition, renal function may be influencedby the release of neurohormones such ascatecholamines, endothelin, or antidi-uretic hormone (ADH) following in-creased intra-abdominal pressure.4Sev-eral studies have reported elevated ADHlevels during i
11、ncreased intra-abdominalpressure,5-8although the actual mecha-nism for this occurrence is poorly under-stood. The major stimuli of ADH secre-tion are an increase in plasma osmolalityand a decrease in the effective circulatoryvolume. Increased ADH secretion pro-motes renal water reabsorption, reduc-i
12、ng plasma osmolality and increasingplasma volume.9However, the clinical sig-nificance of ADH release during pneumo-peritoneum is still unclear.Recently, the laparoscopic approachhas been adopted for the procurement ofa kidney from a living donor for trans-plantation purposes.10Concern has beenraised
13、 about the reported incidence of pri-mary dysfunction of transplanted kid-See Invited Critiqueat end of articleORIGINAL ARTICLEFrom the Departments ofSurgery (Drs Hazebroek,de Vos tot Nederveen Cappel,Bonjer, and IJzermans),Anesthesiology (Dr Gommers),Internal Medicine(Drs van Gelder and Weimar),and
14、 Public Health(Dr Steyerberg), ErasmusMedical Center, Rotterdam,the Netherlands.(REPRINTED) ARCH SURG/ VOL 137, MAY 2002 WWW.ARCHSURG.COM6002002 American Medical Association. All rights reserved.on November 21, 2011 Downloaded from neys after laparoscopic procurement.11To our knowl-edge, no other st
15、udy to date has investigated therelationship between renal function of the donor and re-nal graft and fluctuations in ADH levels.The objectives of this study were to evaluate plasmaADH levels during laparoscopic donor nephrectomy(LDN) and to correlate ADH levels with graft function.RESULTSPatient ch
16、aracteristics and intraoperative data for kid-ney donors are presented in Table 1. There was a sig-nificant difference in body mass index between the 2groups: 25.6 (range, 19-32) for LDN and 32.6 (range,29-37) for ODN (P.001). The 2 groups were similarPATIENTS AND METHODSPATIENT SELECTIONFrom Novemb
17、er 1999 through December 2000, 38 live do-nor nephrectomies were performed. Laparoscopic donornephrectomy, currently the standard approach for this pro-cedure in living donors at our institution, was performedin 32 patients; a conventional open donor nephrectomy(ODN) was performed in 6 patients. The
18、 open procedureswere performed in patients with severe obesity (n=4) ormultiple renal arteries on both sides (n=2).Candidates for donor nephrectomy were thoroughlyscreened using medical history, physical examination, bloodand urine chemistry, immunological studies, and screen-ing for infectious dise
19、ases. Informed consent was ob-tained in all cases. The standard preoperative workup in-cluded renography, Seldinger angiography, and selectiverenal artery angiography in cases of more than one renalartery. Ultrasonography was performed to exclude the pres-ence of kidney deformities. In patients with
20、 normal func-tion and anatomy of both kidneys, the right kidney was pre-ferred for LDN; on the right side, the gonadal and adrenalveins do not insert into the renal vein, making vascular dis-section less time consuming. All LDNs and ODNs were per-formed by a single transplant surgeon (J.N.M.IJ.).Pat
21、ient data were compared for age, sex, body mass in-dex, and American Society of Anesthesiologists score. In alldonors, we documented blood loss, length of operation, meanarterial pressure, and urinary output from time of anesthe-sia induction until nephrectomy. In recipients, mean se-rum creatinine
22、levels at 1, 2, 3, 4, 5, 7, 14, and 28 days aftertransplantation were documented to assess graft function.OPERATIVE TECHNIQUELaparoscopic donor nephrectomy was performed using gen-eral endotracheal anesthesia with the patient in the semi-lateral decubitus position. Details of this procedure havebeen
23、 reported previously.12,13A 30 laparoscope was intro-duced through a Hasson trocar and placed through a smallmidline incision, just caudally to the umbilicus. A pneu-moperitoneum of less than 12 mm Hg was created, and 4additional trocars were inserted. The right nephrectomy wasconducted as follows:
24、mobilization of the right side of thecolon, opening of the renal fascia, and division of the re-nal fat. The renal vein was dissected up to its entrance intothe caval vein and encircled with a rubber vessel loop toenable gentle traction and correct positioning of the sta-pling device. After 5000 U o
25、f heparin were systematicallyadministered, the ureter, renal artery, and renal vein weredivided using a linear vascular laparoscopic stapler (Endo-GIA 30; US Surgical, Norwalk, Conn). The left nephrec-tomy was conducted in a similar fashion: mobilization ofthe left side of the colon and spleen, diss
26、ection of the re-nal vein up to its point of crossing with the aorta, dissec-tion of the renal artery, ligation of the adrenal and ovarianor spermatic veins with titanium clips, dissection of the ure-ter, creation of an extraction incision, anticoagulation,division of the ureter, renal artery, and r
27、enal vein, and ex-traction of the kidney. A plastic extraction bag (Endo-catch; US Surgical) was used to remove the kidney throughthe enlarged subumbilical incision. Directly after kidneyextraction, hemostasis was restored using protamine sul-fate. The kidney was perfused with Eurocollins solution a
28、t4C and stored on ice awaiting transplantation. After clo-sure of the extraction incision, pneumoperitoneum wasreestablished and inspection of the operative field was per-formed. After assurance of adequate hemostasis, the portswere removed using direct visualization, the abdomen wasdesufflated, and
29、 the incisions were closed. Renal transplan-tation was commenced following LDN.HORMONAL MEASUREMENTSBlood samples were obtained after the induction of anes-thesia (T0), 30 minutes after the installation of pneumo-peritoneum (T1), and 90 and 150 minutes after the startof insufflation (T2 and T3, resp
30、ectively). At 30 minutes af-ter abdominal desufflation and extraction of the kidney, an-other sample was obtained (T4). A final blood sample wasobtained 1 day postoperatively (T5). In the 6 ODNs, bloodsamples (approximately 5 mL of blood at each time point)were obtained at similar times. Samples wer
31、e obtained intubes primed with EDTA (K3, 15%; 0.054 mL; 0.34 M/10mL) for the measurement of ADH. Samples were immedi-ately placed on ice and centrifuged for 10 minutes at 4C(3000 rpm), and aliquots were stored at 20C until analy-sis. Antidiuretic hormone was analyzed by radioimmuno-assay using a com
32、mercial kit (Bu hlmann Laboratories, Basel,Switzerland).STATISTICAL ANALYSISStatistical analysis was performed with the supervision ofa statistician (E.W.S.) using SPSS 9.0 statistical software(SPSS Inc, Chicago, Ill). Patients undergoing ODN and LDNwere compared using nonparametric analysis of vari
33、ance(Mann-Whitney U test). The Wilcoxon rank sum test wasused for within-group comparisons. Percentile values (P5,P25,P50,P75, and P95) were calculated for selected patientsat T0 to illustrate the variability and distribution of ADHvalues during donor nephrectomy. Correlations were de-termined betwe
34、en urinary output, plasma ADH concen-trations, and blood pressure readings. Data are summa-rized as meanSEM. PH11021.05 was considered statisticallysignificant.(REPRINTED) ARCH SURG/ VOL 137, MAY 2002 WWW.ARCHSURG.COM6012002 American Medical Association. All rights reserved.on November 21, 2011 Down
35、loaded from regarding all other characteristics. Two patients in theLDN group required conversion to flank laparotomyafter vascular injuries to either the lumbar or renal vein.Data from these patients were excluded from analysis.The mean operative time from skin incision to closurewas similar for bo
36、th groups (168 minutes vs 145 min-utes). Intraoperatively, there were no significant differ-ences regarding estimated blood loss, mean arterialpressure, intravenous volume administration, or uri-nary output.Figure 1A shows plasma ADH levels during LDN.After insufflation (T1), ADH levels were signifi
37、cantlyincreased compared with preinsufflation levels (T0)(PH11021.001). During laparoscopic dissection, ADH levelsremained significantly increased (T2 and T3) (PH11021.001and P=.003, respectively). Thirty minutes after kidneyextraction and subsequent desufflation (T4), ADH lev-els were still signifi
38、cantly higher (PH11021.001). Twenty-four hours after the procedure (T5), plasma ADH levelsdecreased to control values but were still significantlyhigher compared with T0 (P=.003). Figure 1B showsthe plasma ADH concentrations during ODN. Therewere no significant increases in ADH levels during orafter
39、 donor nephrectomy.In Figure 2, percentile values (P5,P25,P50,P75, andP95) of ADH levels during LDN (T0, T1, T2, T3, and T4)are presented. This figure illustrates the large variabilityin plasma ADH concentration during the laparoscopicprocedures and shows that the relative increase in ADHconcentrati
40、on is similar in all percentiles. During al-most the entire duration of the operation, the median value(P50) of the plasma ADH concentration was still withinthe normal range (0.20-4.7 pg/mL 0.19-4.35 pmol/L).In 53% of patients (16/30) who had LDN, the increasein plasma ADH levels during pneumoperito
41、neum was stillwithin this range (data not shown).20100T0 T1 T2 T3 T4 T5Blood SamplesADH, pg/mLK2AK2AK2AK2AMean ADH Levels During LDN20100T0 T1 T2 T3 T4 T5ADH, pg/mLMean ADH Levels During ODNBAFigure 1. A, Plasma antidiuretic hormone (ADH) levels in patients havinglaparoscopic donor nephrectomy (LDN)
42、. T0 indicates preinsufflation;T1, T2, and T3 indicate 30, 90, and 150 minutes after the start of insufflation,respectively; T4, 30 minutes after desufflation; and T5, 24 hours after theprocedure. Data are presented as meanSEM. Asterisks indicate PH11021.05compared with T0. B, Plasma ADH levels in p
43、atients having open donornephrectomy (ODN). T0 indicates before skin incision; T1, 30 minutes afterskin incision; T2, 90 minutes after skin incision; T4, 30 minutes after kidneyextraction; and T5, 24 hours after the procedure. Data are presented asmeanSEM. No value was measured at T3 because of the
44、shorter operatingtime for ODN. Normal values for plasma ADH concentrations range between0.20 and 4.7 pg/mL (0.19-4.35 pmol/L). To convert ADH values to SI units(picomoles per liter), multiply by 0.926.1001000.101234Time Points (T0-T4) During LDNLog 10 Scale, ADH, pg/mLP5P25P50P75P95Distribution of A
45、DH Levels During LDNFigure 2. Percentile values (P5,P25,P50,P75, and P95) of antidiuretic hormone(ADH) levels during laparoscopic donor nephrectomy (LDN) were calculatedat T0 (preinsufflation) to illustrate the large variability in plasma ADHconcentration during the laparoscopic procedures. The loga
46、rithmic scaledemonstrates that during pneumoperitoneum, there is a relative increase inADH concentration compared with T0, which is similar in all percentiles. Inaddition, it shows that during almost the entire length of the operation, themedian value (P50) of plasma ADH is still within the normal r
47、ange (0.20-4.7pg/mL 0.19-4.35 pmol/L). To convert ADH values to SI units (picomolesper liter), multiply by 0.926.Table 1. Patient Characteristics and Operative Datain Kidney Donors*LDN(n = 30)ODN(n=6) P ValueAge, y 50.6 (25-75) 39.5 (24-55) .06Sex, M:F 18:12 4:2 .19Body mass index 25.6 (19-32) 32.6
48、(29-37) H11021.001ASA class, I:II 25:5 4:2 .09Duration of operation,min168 (90-270) 145 (120-175) .19Estimated blood loss, mL 313 (50-1000) 480 (130-1200) .60Mean arterial pressure,mm Hg83 (63-110) 79 (73-85) .81IV fluid hydration,mL/kg per hour21.4 (12.5-42.4) 19.5 (13.8-26.9) .58Urinary outputunti
49、l nephrectomy,mL/kg per hour1.8 (0.5-4.6) 2.0 (0.3-3.5) .79*Data are presented as mean (range) unless otherwise indicated;LDN indicates laparoscopic donor nephrectomy; ODN, open donornephrectomy; ASA, American Society of Anesthesiologists;and IV, intravenous.(REPRINTED) ARCH SURG/ VOL 137, MAY 2002 WWW.ARCHSURG.COM6022002 American Medical Association. All rights reserved.on November 21, 2011 Downloaded from Figure 3A-C shows the results of the regressionanalysis that was performed to investigate if urinary out-put was influenced b
