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Considerations in the patient with diminished renal function
Considerations
in the Patient
Diminished
Renal JOHN
with
Function*
P. MERRILL, M.D.
Boston Massachusetts
ARADOXICALLY the patient with impaired renal function is, if anything, less susceptible to acute severe renal failure during ordinary well managed surgical procedures. It is difficult to document this statement since the incidence of acute renal failure is so unpredictable in people with normal renal function. Patients with severe prolonged hypotension during surgical procedures may have little or nothing in the way of residual renal damage whereas others with mild gastrointestinal hemorrhage may develop acute renal failure. From the welter of conflicting experimental and clinical evidence that relates to the etiology of acute renal failure, one or two pertinent facts emerge. Acute tubular necrosis leading to acute renal failure appears to depend upon some degree of shunting of blood away from the kidney, possibly by way of the juxtamedullary glomeruli. This shunting in turn appears to depend upon active vasomotion rather than ischemia alone. It is possible, for instance, to completely sever the blood supply (and also the neural supply) to the kidney of an identical twin donor for 45 to 50 minutes and have urinary flow resume immediately when the kidney is successfully anastamosed to the recipient’s blood vessels. On the other hand, less than 20 minutes of profound hypotension in an individual with intact kidneys is apt to result in acute renal failure. It has been suggested that the difference represents the sequence of vasoconstriction, resumption of blood supply and edema.’ It is well documented that oliguria and decreased urinary flow predispose to acute renal failure. The effects of anesthesia and trauma in stimulating antidiuretic hormone are well known and for this reason may predispose to acute renal failure of the normal kidney. In-
terestingly enough, all of these factors appear less operative in the patient with some degree of renal functional impairment. The major characteristic of a kidney with functional impairment is decreased flexibility to any stimulus. Frequently, sclerotic arterioles and arteries in such kidneys are less flexible in their response to vasomotor stimuli. Destruction of renal parenchyma in renal disease, whatever its cause, usually proceeds by a sequence of events which results in destruction of total nephrons and resultant hypertrophy of the remaining units. In these residual “intact nephrons” the urinary flow is probably higher and the blood supply greater per nephron than in normal nephron. It is well known that persons with early renal failure cannot concentrate their urine and do not respond to antidiuretic hormone either exogenous or endogenous. In a sense, therefore, they. are protected against these facilitating factors. It has been suggested that since the total load of solute excreted in 24 hours is identical to that excreted by the normal person, that these residual hypertrophied “intact nephrons” must excrete more solute per nephron and therefore are undergoing a solute diuresis.2 It has been demonstrated that the effect of the infusion of the mannitol, which produces a solute diuresis in the normal individual, will prevent acute renal failure in the experimental animal3 (and probably the human”) under conditions In a which tend to produce this condition. sense, then, the patient with renal functional impairment is already undergoing his own solute diuresis. Obviously, however, hypotension should be as assiduously avoided in patients with renal functional impairment as in anyone else. It remains a fact, however, that there is no good evidence to suggest that people with impaired
P
*From the Cardiorenal Laboratory, Peter Bent Brigham Hospital, and ,Medical School, Boston, Mass. 640
the
THE
Department of Medicine, Harvard AMERICAN
JOURNAL
OF CARDIOLOGY
Patient
with
l>iminished
Kenal
641
Function
BLOOD UREA NITRCKJEN mg./lOO ml. 170-
?
150 130 110 04V Of 90 70 -
IO -
lCIIITONLAL
2
4
6
OIALVSIS
6
IO
PCllTONRAL I 6 I
I2
14
16
.
DIALYSIS I . I
I6
20
1
22
.
I
24
.
I
.
26
DAY IN HOSPITAL
FIG. I. Clinical course of a patient with severe renal failure prior transplant. renal function are more susceptible to acute severe renal failure during surgical procedures When proper prethan are normal individuals. and postoperative care and anesthetic management are employed, our own experience coincides with that of Hamburger who, in reporting 200 cases of postoperative renal failure, notes the surprisingly low incidence of postoperative complications in patients with pre-existing renal failure when adequate precautions are observed before, during and after operation.” PRE- AND POSTOPERATIVEMANAGEMENT Patients with Impaired Renal Function: All of the foregoing, however, relates primarily to the operative procedure. It is important to consider pre- and postoperative management in patients with impairment of renal function. It has been stated that patients with renal functional impairment are less “flexible” than normal individuals. I mean by this that although eventually they may respond to a water load or may decrease urinary volume as a response to water restriction, this occurs slowly and less flexibly. Thus preoperative restriction of fluids with continuing renal losses thereof may result in total dehydration which may in turn predispose the patient to renal damage during surgery. The response of the normal kidney to NOVEMBER
1963
to successful renal
operative trauma is a cutback in the excretion of water and sodium. However, the normally hydrated patient with renal functional impairment may not be able to decrease water and sodium excretion in response to the normal stimuli of operative trauma. If, as has been suggested, G the trauma of surgery creates a “third space” in which sodium and water may be sequestered, patients with renal functional impairment may have both internal and external losses of electrolytes which require replacement to maintain adequate intravascular volume. Thus, management of the postoperative patient should not necessarily require restriction of sodium and water in the early postoperative phase but should be carefully regulated according to particular electrolyte and water losses. There is some evidence to suggest that a certain percentage of persons with normal renal function may be unable to concentrate their urine in the postoperative period.7 Patients with Severe Impairment of Cardiac Fumtion: These patients constitute a special group about whom much has been written. The group with cardiac failure may have marked decreases in glomerular filtration rate and renal plasma flow which pertain to impairment of cardiac output rather than renal parenchymal damage. During or a few days following cor-
642
Merrill
recti1.e surgery, antidiuretic stimuli and further impairment of cardiac output ma)- severely irnpair renal function with marked retention of urea, sodium and water. The result is oliguria, nitrogen retention and, as water is retained in excess of solute, hyponatremia.6 Characteristically such persons may ha\re a urinary volume of less than 400 ml.,/day. Unlike the patient with similar urinary volume who is suffering from acute tubular necrosis, however, the ostnolality of the urine tends to be higher than that of plasma, i.e., the urine is more concentrated; the sodium concentration is less than 30 mEq.,‘L. whereas with full blown tubular necrosis it is generally higher. With improvement of cardiac function spontaneous diuresis ensues, and the urine becomes more dilute as the retained water is excreted. The blood urea nitrogen drops, and the hyponatremia is corrected without the provision of exogenous sodium. As has been frequent11 stressed, the correction of hyponatremia under these circumstances is to he accomplished not by the administration of sodium-containingsolutions, but by restriction of water. Patients zuith Uremia: In recent )-ears, extensive experience has accrued in the surgery of patients with severe renal failure and marked Interestingly again, such patients “uremia.” tolerate surgical procedures surprisingly well if careful attention to anesthesia and hydration is given. At first glance patients with uremia should be distressingly poor surgical risks. Frequently they are hypertensive; they have problems of bleeding and clotting,“,‘” abnormalities of glucose metabolism”~‘~ as well as abnormalities of the central nervous system13 and cardiac function.2 Most of them are anemic. In spite of this bizzarC concoctation of contraindications to surgery, extensive surgical procedures have been successfully performed on severely uremic patients during kidney transplantation.‘l The choice of anesthesia is important.15 Possibly the fact that such patients are chronically ill and have a decreased catabolic response to surgery is advantageous. Our ability to treat uremia with the artificial kidney and with peritoneal irrigation undoubtedly enables US to prepare for surgery patients who would not tolerate such procedures previously. Figure 1 illustrates the course of a 23 year old patient with severe chronic renal failure. On admission to another hospital, his blood urea nitroHe was treated twice with the gen was 340 mg.%. artificial kidney before transfer to the Peter Bent
Brigham Hospital. For the 10 days before transfer he was almost totally anuric and remained so until successful transplantation of a normal kidney from his identical twin brother. His course in the hospital was complicated by suppurative pericarditis which required pericardiostomy and open drainage. In addition to this, he had a staphylococcal septicemia: pneumonia of the left lower lobe, a large decubitus ulcer requiring drainage, toxic psychosis, melena and hemorrhagic cystitis. In spite of these complications, he survived almost a month of total anuria and recovered following a successful renal homograft. On the second hospital day hemodialysis was performed and following that, peritoneal dialysis was continued for one week. The marked rise in blood urea nitrogen during the two-day omission of peritoneal dialysis should be noted a~ well as the drop following re-institution of this procedure. The blood urea nitrogen on the day of operation was 24 mg., and the patient tolerated the procedure with a little difficulty. Postoperatively he required pericardiectomy for constrictive pericarditis but is alive and well one year after the procedure. SUMMARY
Knowledge of the renal functional defect and the application of corrective fluid and electrolyte therapy make it possible to operate on patients with minimal functional impairment without increasing operative morbidity. Extensive surgical procedures are possible in patients with severe uremia if careful attention is paid to anesthesia and fluid replacement. The use of extrarenal methods of treatin
postopera-
6. BOBA, A. and LANDMESSER, C. M. Renal complicaAnesthetions after anesthesia and operation. siology, 22: 781, 1961. 7. GULLICK, H. D. and RAISZ, L. G.
Changes
in
‘I‘IIE AMERICANJOURNAL OF CARDIOLOGY
Patient
8.
3.
10.
11.
with I~iminisl~ed Renal
renal concentrating ability associated with major surgical procedurrs. :Vew En,&nd J. Med., 262: 1309, 1960. WILSON, G. M. et al. Metabolic changes associated with mitral valvuloplasty. Circulation, 9 : 199. 1954. I,ew~s, .I. I-I., ZUCKIIK, M. B. and FERGUSON, J. H. Bleeding tcndencit-s in uremia. Hood, 11: 1073, 1956. GEIGER, M. ‘I‘., RATH, C. C. and CHUNG, A. C. Evidence for a qualitative platelet defect in uremia. CLz?z.Res., 7: 212, 1959. COHEN., B. D. Abnormal carbohydrate metabolism in renal disease: blood glucose unresponsiveness
NOVEMBER1963
633
Function
to hypoglycemia,
epinephrine
and glrrcu~on.
.4nrr.
ht. Med., 57: 204, 1962. 12. ~VLTESTERVELT, F. B., JR. and SCIIREINER,G. 11. Thr intolerancr of urrmir patients. carbohydrate ;Inri. Inl. .\lrd., 57: 266, 1962. 13. I.OCKE, S., MERRILL, .J. and TVI.I:K, 11. K. Nrurolo+c
complications
of acutc
urrmia.
.4rch.
Irr/.
AWed., 108: 519, 1761. 14. hfLTRRA’I.3 .J. F,.. bkRRILI., J P. and HARRISOK, .I. II. Kidney transplantation between 7 pairs cf idrntical twins. .4nn. S’urg., 148: 343, 1958. 15. VPINDAM.1.. D.. HARRISON, .I.H., MURRAY, .J. and MERRILL, J. P. Anrsthrtic aspects of renal homoti.ansplantation
in man.
.4nrs/hsvroloyv (in
press).
in the Patient
Diminished
Renal JOHN
with
Function*
P. MERRILL, M.D.
Boston Massachusetts
ARADOXICALLY the patient with impaired renal function is, if anything, less susceptible to acute severe renal failure during ordinary well managed surgical procedures. It is difficult to document this statement since the incidence of acute renal failure is so unpredictable in people with normal renal function. Patients with severe prolonged hypotension during surgical procedures may have little or nothing in the way of residual renal damage whereas others with mild gastrointestinal hemorrhage may develop acute renal failure. From the welter of conflicting experimental and clinical evidence that relates to the etiology of acute renal failure, one or two pertinent facts emerge. Acute tubular necrosis leading to acute renal failure appears to depend upon some degree of shunting of blood away from the kidney, possibly by way of the juxtamedullary glomeruli. This shunting in turn appears to depend upon active vasomotion rather than ischemia alone. It is possible, for instance, to completely sever the blood supply (and also the neural supply) to the kidney of an identical twin donor for 45 to 50 minutes and have urinary flow resume immediately when the kidney is successfully anastamosed to the recipient’s blood vessels. On the other hand, less than 20 minutes of profound hypotension in an individual with intact kidneys is apt to result in acute renal failure. It has been suggested that the difference represents the sequence of vasoconstriction, resumption of blood supply and edema.’ It is well documented that oliguria and decreased urinary flow predispose to acute renal failure. The effects of anesthesia and trauma in stimulating antidiuretic hormone are well known and for this reason may predispose to acute renal failure of the normal kidney. In-
terestingly enough, all of these factors appear less operative in the patient with some degree of renal functional impairment. The major characteristic of a kidney with functional impairment is decreased flexibility to any stimulus. Frequently, sclerotic arterioles and arteries in such kidneys are less flexible in their response to vasomotor stimuli. Destruction of renal parenchyma in renal disease, whatever its cause, usually proceeds by a sequence of events which results in destruction of total nephrons and resultant hypertrophy of the remaining units. In these residual “intact nephrons” the urinary flow is probably higher and the blood supply greater per nephron than in normal nephron. It is well known that persons with early renal failure cannot concentrate their urine and do not respond to antidiuretic hormone either exogenous or endogenous. In a sense, therefore, they. are protected against these facilitating factors. It has been suggested that since the total load of solute excreted in 24 hours is identical to that excreted by the normal person, that these residual hypertrophied “intact nephrons” must excrete more solute per nephron and therefore are undergoing a solute diuresis.2 It has been demonstrated that the effect of the infusion of the mannitol, which produces a solute diuresis in the normal individual, will prevent acute renal failure in the experimental animal3 (and probably the human”) under conditions In a which tend to produce this condition. sense, then, the patient with renal functional impairment is already undergoing his own solute diuresis. Obviously, however, hypotension should be as assiduously avoided in patients with renal functional impairment as in anyone else. It remains a fact, however, that there is no good evidence to suggest that people with impaired
P
*From the Cardiorenal Laboratory, Peter Bent Brigham Hospital, and ,Medical School, Boston, Mass. 640
the
THE
Department of Medicine, Harvard AMERICAN
JOURNAL
OF CARDIOLOGY
Patient
with
l>iminished
Kenal
641
Function
BLOOD UREA NITRCKJEN mg./lOO ml. 170-
?
150 130 110 04V Of 90 70 -
IO -
lCIIITONLAL
2
4
6
OIALVSIS
6
IO
PCllTONRAL I 6 I
I2
14
16
.
DIALYSIS I . I
I6
20
1
22
.
I
24
.
I
.
26
DAY IN HOSPITAL
FIG. I. Clinical course of a patient with severe renal failure prior transplant. renal function are more susceptible to acute severe renal failure during surgical procedures When proper prethan are normal individuals. and postoperative care and anesthetic management are employed, our own experience coincides with that of Hamburger who, in reporting 200 cases of postoperative renal failure, notes the surprisingly low incidence of postoperative complications in patients with pre-existing renal failure when adequate precautions are observed before, during and after operation.” PRE- AND POSTOPERATIVEMANAGEMENT Patients with Impaired Renal Function: All of the foregoing, however, relates primarily to the operative procedure. It is important to consider pre- and postoperative management in patients with impairment of renal function. It has been stated that patients with renal functional impairment are less “flexible” than normal individuals. I mean by this that although eventually they may respond to a water load or may decrease urinary volume as a response to water restriction, this occurs slowly and less flexibly. Thus preoperative restriction of fluids with continuing renal losses thereof may result in total dehydration which may in turn predispose the patient to renal damage during surgery. The response of the normal kidney to NOVEMBER
1963
to successful renal
operative trauma is a cutback in the excretion of water and sodium. However, the normally hydrated patient with renal functional impairment may not be able to decrease water and sodium excretion in response to the normal stimuli of operative trauma. If, as has been suggested, G the trauma of surgery creates a “third space” in which sodium and water may be sequestered, patients with renal functional impairment may have both internal and external losses of electrolytes which require replacement to maintain adequate intravascular volume. Thus, management of the postoperative patient should not necessarily require restriction of sodium and water in the early postoperative phase but should be carefully regulated according to particular electrolyte and water losses. There is some evidence to suggest that a certain percentage of persons with normal renal function may be unable to concentrate their urine in the postoperative period.7 Patients with Severe Impairment of Cardiac Fumtion: These patients constitute a special group about whom much has been written. The group with cardiac failure may have marked decreases in glomerular filtration rate and renal plasma flow which pertain to impairment of cardiac output rather than renal parenchymal damage. During or a few days following cor-
642
Merrill
recti1.e surgery, antidiuretic stimuli and further impairment of cardiac output ma)- severely irnpair renal function with marked retention of urea, sodium and water. The result is oliguria, nitrogen retention and, as water is retained in excess of solute, hyponatremia.6 Characteristically such persons may ha\re a urinary volume of less than 400 ml.,/day. Unlike the patient with similar urinary volume who is suffering from acute tubular necrosis, however, the ostnolality of the urine tends to be higher than that of plasma, i.e., the urine is more concentrated; the sodium concentration is less than 30 mEq.,‘L. whereas with full blown tubular necrosis it is generally higher. With improvement of cardiac function spontaneous diuresis ensues, and the urine becomes more dilute as the retained water is excreted. The blood urea nitrogen drops, and the hyponatremia is corrected without the provision of exogenous sodium. As has been frequent11 stressed, the correction of hyponatremia under these circumstances is to he accomplished not by the administration of sodium-containingsolutions, but by restriction of water. Patients zuith Uremia: In recent )-ears, extensive experience has accrued in the surgery of patients with severe renal failure and marked Interestingly again, such patients “uremia.” tolerate surgical procedures surprisingly well if careful attention to anesthesia and hydration is given. At first glance patients with uremia should be distressingly poor surgical risks. Frequently they are hypertensive; they have problems of bleeding and clotting,“,‘” abnormalities of glucose metabolism”~‘~ as well as abnormalities of the central nervous system13 and cardiac function.2 Most of them are anemic. In spite of this bizzarC concoctation of contraindications to surgery, extensive surgical procedures have been successfully performed on severely uremic patients during kidney transplantation.‘l The choice of anesthesia is important.15 Possibly the fact that such patients are chronically ill and have a decreased catabolic response to surgery is advantageous. Our ability to treat uremia with the artificial kidney and with peritoneal irrigation undoubtedly enables US to prepare for surgery patients who would not tolerate such procedures previously. Figure 1 illustrates the course of a 23 year old patient with severe chronic renal failure. On admission to another hospital, his blood urea nitroHe was treated twice with the gen was 340 mg.%. artificial kidney before transfer to the Peter Bent
Brigham Hospital. For the 10 days before transfer he was almost totally anuric and remained so until successful transplantation of a normal kidney from his identical twin brother. His course in the hospital was complicated by suppurative pericarditis which required pericardiostomy and open drainage. In addition to this, he had a staphylococcal septicemia: pneumonia of the left lower lobe, a large decubitus ulcer requiring drainage, toxic psychosis, melena and hemorrhagic cystitis. In spite of these complications, he survived almost a month of total anuria and recovered following a successful renal homograft. On the second hospital day hemodialysis was performed and following that, peritoneal dialysis was continued for one week. The marked rise in blood urea nitrogen during the two-day omission of peritoneal dialysis should be noted a~ well as the drop following re-institution of this procedure. The blood urea nitrogen on the day of operation was 24 mg., and the patient tolerated the procedure with a little difficulty. Postoperatively he required pericardiectomy for constrictive pericarditis but is alive and well one year after the procedure. SUMMARY
Knowledge of the renal functional defect and the application of corrective fluid and electrolyte therapy make it possible to operate on patients with minimal functional impairment without increasing operative morbidity. Extensive surgical procedures are possible in patients with severe uremia if careful attention is paid to anesthesia and fluid replacement. The use of extrarenal methods of treatin
postopera-
6. BOBA, A. and LANDMESSER, C. M. Renal complicaAnesthetions after anesthesia and operation. siology, 22: 781, 1961. 7. GULLICK, H. D. and RAISZ, L. G.
Changes
in
‘I‘IIE AMERICANJOURNAL OF CARDIOLOGY
Patient
8.
3.
10.
11.
with I~iminisl~ed Renal
renal concentrating ability associated with major surgical procedurrs. :Vew En,&nd J. Med., 262: 1309, 1960. WILSON, G. M. et al. Metabolic changes associated with mitral valvuloplasty. Circulation, 9 : 199. 1954. I,ew~s, .I. I-I., ZUCKIIK, M. B. and FERGUSON, J. H. Bleeding tcndencit-s in uremia. Hood, 11: 1073, 1956. GEIGER, M. ‘I‘., RATH, C. C. and CHUNG, A. C. Evidence for a qualitative platelet defect in uremia. CLz?z.Res., 7: 212, 1959. COHEN., B. D. Abnormal carbohydrate metabolism in renal disease: blood glucose unresponsiveness
NOVEMBER1963
633
Function
to hypoglycemia,
epinephrine
and glrrcu~on.
.4nrr.
ht. Med., 57: 204, 1962. 12. ~VLTESTERVELT, F. B., JR. and SCIIREINER,G. 11. Thr intolerancr of urrmir patients. carbohydrate ;Inri. Inl. .\lrd., 57: 266, 1962. 13. I.OCKE, S., MERRILL, .J. and TVI.I:K, 11. K. Nrurolo+c
complications
of acutc
urrmia.
.4rch.
Irr/.
AWed., 108: 519, 1761. 14. hfLTRRA’I.3 .J. F,.. bkRRILI., J P. and HARRISOK, .I. II. Kidney transplantation between 7 pairs cf idrntical twins. .4nn. S’urg., 148: 343, 1958. 15. VPINDAM.1.. D.. HARRISON, .I.H., MURRAY, .J. and MERRILL, J. P. Anrsthrtic aspects of renal homoti.ansplantation
in man.
.4nrs/hsvroloyv (in
press).