Letters to the Editor
To the Editor: We have read with interest the review of Drs. Wait and Kahng [1] and would like to make a short comment on their support of the use of mannitol as a measure to prevent postoperative renal failure in patients with obstructive jaundice. Dawson [2] first reported the ability of mannitol to prevent the decrease in effective renal blood flow and creatinine clearance in the postoperative period of patients operated on for obstructive jaundice. However, his results are statistically questionable, have not been confirmed by other groups, and the only prospective and randomized study, not quoted by Drs. Wait and Kahng, concerning the efficacy of this osmotic diuretic gave negative results [3]. In this trial, we showed that mannitol did not improve renal function in jaundiced patients and that in some instances it could have contributed to worsen it. The mean preoperative creatinine clearance of patients receiving mannitol was 71 mL/min, which dropped to 57 m L / m i n after surgery (p = 0.037). In the no-mannitol group, the mean preoperative creatinine clearance was 64 m L / min, which dropped to 54 m L / m i n after surgery, the difference not being statistically significant. The main reason why mannitol does not improve renal function in this setting may be preexistent volume depletion associated with obstructive jaundice, as was first suggested by Williams et al [4]. That volume depletion may play a prominent role in the renal failure complicating obstructive jaundice is now supported by an experimental study carried out in our laboratory [5] in which we measured the bodyfluid compartments of rabbits 6 and 12 days after common bile duct ligation by a multi-isotope dilution technique. In jaundiced animals, a 24% decrease of extracellular water was observed at day 6 and a 35% decrease at day 12, No appreciable changes
444
were detected in sham-operated animals. At day 12, a 15% reduction of plasma volume was also observed. The disturbances in renal function and body composition could be reproduced in a control group of pairfed and pair-drunk sham-operated animals. Although studies in humans with obstructive jaundice are yet to be undertaken to prove volume depletion in the clinical setting, we do not recommend the use of mannitol as a prophylactic measure to prevent renal failure in obstructive jaundice. It has not shown clear benefits and may aggravate depletion of the extracell'ular w a t e r c o m p a r t m e n t . From data drawn from our clinical and experimental experience, we favor the hypothesis that the keystone in the pathogenesis of renal failure complicating obstructive jaundice is volume depletion and that this is the basis for the increased sensitivity of the "jaundiced kidney" to hypovolemia, hypotension, vasoactive hormones, endotoxin, or nephrotoxic drugs.
In Response: We appreciate the comments o-f Drs. Gubern, Martinez-R6denas, and Sitges-Serra. We agree with these authors that volume depletion may be one of several factors that contributes to the renal dysfunction complicating obstructive jaundice. McPherson et al [I] have previously demonstrated that preoperative creatinine clearance in jaundiced patients i m p r o v e d with h y d r a t i o n alone. With this in mind, we had some reservations about the study performed by Gubern and associates [2] in which they were unable to demonstrate any protective effect of mannitol in patients with obstructive jaundice. First, the types of operative procedures were not evenly distributed between the two study groups. Second, creatinine clearance data were not given for all patients in the study. Third, no information regarding volume status, e.g., cell volume profile or Swan-Ganz catheter readings, and only minimal information regarding fluid management were inJ . n a Gubern, MD cluded. Fourth, in these studies, Hospital General de Sabadell mannitol was continued for 2 days Barcelona, Spain postoperatively. We agree that this practice may indeed lead to volume F. Martfnez-Rbdenas, MD depletion. Because of these issues, we A. Sitges-Serra, MD are unconvinced that the authors Hospital Universitario del Mar have demonstrated that mannitol has Universitat Aut6noma de Barcelona no beneficial effect on postoperative Barcelona, Spain renal function in the patient with obstructive jaundice. We agree with 1. Wait RB, Kahng KU. Renal failure com- these authors that a well-planned, plicating obstructive jaundice. Am J Surg randomized, blinded, prospective 1989; 157: 256-63. study will be necessary to definitively 2. Dawson JL. Postoperativerenal function assess the efficacy of mannitol in in obstructivejaundice: effect of a mannitol ameliorating postoperative declines diuresis. Br Med J 1965; 1: 82-6. 3. Gubern JM. Sancho J J, Sim6 J, Sitges- in renal function. However, in the abSerra A. A randomized trial on the effect of sence of solid evidence that mannitol mannitol on postoperativerenal function in is detrimental, as these authors sugpatients with obstructivejaundice. Surgery gest, it appears reasonable to con1988: 103: 39-44. 4. Williams RD, Elliot DW, Zollinger RM. tinue administering mannitol at least The effect of hypotension in obstructive preoperatively on the basis of both jaundice. Arch Surg 1960; 81: 331-40. the clinical and laboratory work re5. Martinez-R6denas F. Oms L. Carulla X. ported by Dawson [3-5]. Segura M, Sancho J J, Sitges-SerraA. MeaWhile we agree with Martinezsurement of body water compartmentsafter ligation of the common bile duct in the rab- R&lenas and co-workers that uncorrected volume depletion can contribbit. Br J Surg 1989; 76: 461-4.
THE AMERICAN JOURNAL OF SURGERY VOLUME 159 APRIL 1990
To the Editor: We have read with interest the review of Drs. Wait and Kahng [1] and would like to make a short comment on their support of the use of mannitol as a measure to prevent postoperative renal failure in patients with obstructive jaundice. Dawson [2] first reported the ability of mannitol to prevent the decrease in effective renal blood flow and creatinine clearance in the postoperative period of patients operated on for obstructive jaundice. However, his results are statistically questionable, have not been confirmed by other groups, and the only prospective and randomized study, not quoted by Drs. Wait and Kahng, concerning the efficacy of this osmotic diuretic gave negative results [3]. In this trial, we showed that mannitol did not improve renal function in jaundiced patients and that in some instances it could have contributed to worsen it. The mean preoperative creatinine clearance of patients receiving mannitol was 71 mL/min, which dropped to 57 m L / m i n after surgery (p = 0.037). In the no-mannitol group, the mean preoperative creatinine clearance was 64 m L / min, which dropped to 54 m L / m i n after surgery, the difference not being statistically significant. The main reason why mannitol does not improve renal function in this setting may be preexistent volume depletion associated with obstructive jaundice, as was first suggested by Williams et al [4]. That volume depletion may play a prominent role in the renal failure complicating obstructive jaundice is now supported by an experimental study carried out in our laboratory [5] in which we measured the bodyfluid compartments of rabbits 6 and 12 days after common bile duct ligation by a multi-isotope dilution technique. In jaundiced animals, a 24% decrease of extracellular water was observed at day 6 and a 35% decrease at day 12, No appreciable changes
444
were detected in sham-operated animals. At day 12, a 15% reduction of plasma volume was also observed. The disturbances in renal function and body composition could be reproduced in a control group of pairfed and pair-drunk sham-operated animals. Although studies in humans with obstructive jaundice are yet to be undertaken to prove volume depletion in the clinical setting, we do not recommend the use of mannitol as a prophylactic measure to prevent renal failure in obstructive jaundice. It has not shown clear benefits and may aggravate depletion of the extracell'ular w a t e r c o m p a r t m e n t . From data drawn from our clinical and experimental experience, we favor the hypothesis that the keystone in the pathogenesis of renal failure complicating obstructive jaundice is volume depletion and that this is the basis for the increased sensitivity of the "jaundiced kidney" to hypovolemia, hypotension, vasoactive hormones, endotoxin, or nephrotoxic drugs.
In Response: We appreciate the comments o-f Drs. Gubern, Martinez-R6denas, and Sitges-Serra. We agree with these authors that volume depletion may be one of several factors that contributes to the renal dysfunction complicating obstructive jaundice. McPherson et al [I] have previously demonstrated that preoperative creatinine clearance in jaundiced patients i m p r o v e d with h y d r a t i o n alone. With this in mind, we had some reservations about the study performed by Gubern and associates [2] in which they were unable to demonstrate any protective effect of mannitol in patients with obstructive jaundice. First, the types of operative procedures were not evenly distributed between the two study groups. Second, creatinine clearance data were not given for all patients in the study. Third, no information regarding volume status, e.g., cell volume profile or Swan-Ganz catheter readings, and only minimal information regarding fluid management were inJ . n a Gubern, MD cluded. Fourth, in these studies, Hospital General de Sabadell mannitol was continued for 2 days Barcelona, Spain postoperatively. We agree that this practice may indeed lead to volume F. Martfnez-Rbdenas, MD depletion. Because of these issues, we A. Sitges-Serra, MD are unconvinced that the authors Hospital Universitario del Mar have demonstrated that mannitol has Universitat Aut6noma de Barcelona no beneficial effect on postoperative Barcelona, Spain renal function in the patient with obstructive jaundice. We agree with 1. Wait RB, Kahng KU. Renal failure com- these authors that a well-planned, plicating obstructive jaundice. Am J Surg randomized, blinded, prospective 1989; 157: 256-63. study will be necessary to definitively 2. Dawson JL. Postoperativerenal function assess the efficacy of mannitol in in obstructivejaundice: effect of a mannitol ameliorating postoperative declines diuresis. Br Med J 1965; 1: 82-6. 3. Gubern JM. Sancho J J, Sim6 J, Sitges- in renal function. However, in the abSerra A. A randomized trial on the effect of sence of solid evidence that mannitol mannitol on postoperativerenal function in is detrimental, as these authors sugpatients with obstructivejaundice. Surgery gest, it appears reasonable to con1988: 103: 39-44. 4. Williams RD, Elliot DW, Zollinger RM. tinue administering mannitol at least The effect of hypotension in obstructive preoperatively on the basis of both jaundice. Arch Surg 1960; 81: 331-40. the clinical and laboratory work re5. Martinez-R6denas F. Oms L. Carulla X. ported by Dawson [3-5]. Segura M, Sancho J J, Sitges-SerraA. MeaWhile we agree with Martinezsurement of body water compartmentsafter ligation of the common bile duct in the rab- R&lenas and co-workers that uncorrected volume depletion can contribbit. Br J Surg 1989; 76: 461-4.
THE AMERICAN JOURNAL OF SURGERY VOLUME 159 APRIL 1990
