DIALYTIC TREATMENT OF RHABDOMYOLYSIS-INDUCED ACUTE RENAL FAILURE: OUR EXPERIENCE

Abstract

Acute renal failure is the most common complication of rhabdomyolysis, with an 8–20% reported incidence. In particular, rhabdomyolysis associated with acute renal failure is frequently observed in critically ill patients, with a 6–16% reported incidence in Intensive Care Units. Dialytic treatment is necessary to correct hydroelectrolytic imbalance and renal function alterations and it may be a pathogenetic therapy by myoglobin removal. In the present study we evaluated our experience on patients suffering from rhabdomyolysis and acute renal failure subjected to dialytic treatment. We retrospectively studied 28 patients, 17 admitted in our Intensive Care Unit (ICU-patients) and treated by continuous renal replacement therapy (particularly by continuous venovenous hemofiltration, continuous venovenous hemodialysis and continuous venovenous hemodiafiltration) and 11 admitted in our Nephrology Department (NICU-patients) and treated by high-efficiency daily hemodialysis. We excluded one ICU-patient from the study because she was affected with lung end-stage neoplasia and it would have been difficult to evaluate the effects of the dialytic treatment on RML biochemical index and on her final outcome. ICU-patients were older, with a mean age of 64 ± 10 yrs, and were suffering from MODS and typical elderly diseases, such as cardiac and respiratory chronic failure, except from 3 patients with acute liver failure resulting from poisoning, who were relatively younger. In NICU-patients, instead, the mean age was 36 ± 16 yrs and the causes of RML were narcotic drugs abuse, repetitive seizures and vigorous exercise, more frequently observed in young people. In three relatively older NICU-patients RML was due to lipid lowering drugs assumption. Before starting the dialytic treatment, in ICU-patients CPK plasma level was 2615 ± 3586, while K⁺ was 5.10 ± 1.08 and sCr was 5.69 ± 4.06 In NICU-patients, on the other hand, CPK was 14273 ± 9266, while K⁺ was 5,75 ± 0.92 and sCr was 5,9 ± 0.4.

ICU-patients mortality rate was 50% (8/16 patients) in spite of the good recovery of renal function and the biochemical RML indexes improvement. In NICU-patients, instead, only one patient died for septic complications (he was a heroin-addict and suffered from overdose syndrome). Early dialytic treatment of RML allows not only to avoid life-threatening complications (first of all the acute renal failure) but moreover it's a pathogenetic treatment because it removes great amount of myoglobin from the plasma. Beside this, continuous renal replacement therapy allows a successful management of critically ill patients with severe hemodynamic conditions. Nevertheless, the final outcome may be very different between ICU- and NICU-patients, with a higher mortality rate in ICU-patients, suffering from MODS.

INTRODUCTION

Rhabdomyolysis (RML) may result from very different causes and consists of a clinical picture made of general and muscular symptoms, with the passage of enzymatic, metabolic and electrolytic components, in particular myoglobin, from the internal muscle to circulating blood. This is the main cause of the renal damage, which in 8–20% of cases is associated with RML [[1]]. Particularly, RML associated with acute renal failure (ARF) is frequently observed in the Intensive Care Unit (ICU), with an incidence of 6–16% in such a department [[2]]. In ICU patients we can often find a multiorgan dysfunction syndrome (MODS), with a very poor prognosis worsened by the rhabdomyolytic syndrome: previous literature describes a 75% mortality in patients suffering from MODS, ARF and RML vs. 44.3% in patients suffering from MODS and ARF but without RML [[3]]. The dialytic treatment is necessary to correct hydroelectrolytic imbalance and renal dysfunction [[4]].

In this study we describe our experience on 28 patients suffering from ARF and RML subjected to dialytic treatment.

PATIENTS AND METHODS

We retrospectively studied 28 patients suffering from ARF and RML, admitted into our Medical Center between January 1991 and December 1999. Among these patients, 17 (ICU-patients) suffered from MODS with ARF and RML and were hospitalized in the ICU. We excluded one of these patients from the study because affected with lung end-stage neoplasia and it would have been difficult to evaluate the effects of the dialytic treatment on RML biochemical index and on her final outcome. The remaining 11 patients had ARF and RML without MODS and were not ICU patients (NICU-patients). In Table 1 patients clinical data are shown.

Table 1. Patients' Clinical Data

Pt N°	Sex	Age	Cause	MOFS	Treatment
1	M	70	LLD^1	No	HHD^2
2	F	35	HO^3	No	HHD
3	M	26	MA^4	No	HHD
4	M	19	HO	No	HHD
5	F	34	HO	No	HHD
6	F	53	LLD	No	HHD
7	F	31	HO	No	HHD
8	M	19	HO	No	HHD
9	M	33	HO	No	HHD
10	M	22	RS^5	No	HHD
11	M	55	LLD	No	HHD
12	M	69	AMI^6	Yes	CVVH^7
13	M	64	ALF^8	Yes	CVVHD^9
14	M	70	AMI	Yes	CVVH
15	M	61	Shock	Yes	CVVH
16	M	40	ALF	Yes	CVVHD
17	M	74	AMI	Yes	CVVHD
18	M	59	ALF	Yes	CVVHD
19	M	64	AMI	Yes	CVVHD
20	M	68	AMI	Yes	CVVHD
21	M	67	Ictus cerebri	Yes	CVVH
22	M	53	Poisoning	Yes	CVVHDF^10
23	F	79	ARDS^11	Yes	CVVHD
24	M	82	ARDS	Yes	CVVH
25	F	52	AMI	Yes	CVVH
26	M	51	ARDS	Yes	CVVHD
27	F	61	ALF	Yes	CVVHDF
28	F	70	Lung neoplasia	Yes	CVVHD

¹LLD: Lipid-lowering drugs.

²HHD: High-efficiency hemodialysis.

³HO: Heroin overdose.

⁴MA: Muscular activity.

⁵RS: Repetitive seizures.

⁶AMI: Acute myocardial infarction.

⁷CVVH: Continuous venovenous hemofiltration.

⁸ALF: Acute liver failure.

⁹CVVHD: Continuous venovenous hemodialysis.

¹⁰CVVHDF: Continuous venovenous hemodiafiltration.

¹¹ARDS: Acute respiratory distress syndrome.

In ICU-patients MODS was diagnosed according to Sauaia's criteria [[5]] while the presence of a systemic inflammatory response syndrome (SIRS) was identified by ACCP/SCCM criteria [[6]]. We also evaluated patients' clinical conditions using the APACHE II score as a prognostic index (mean value: 29 ± 7) [[7]]. The dialytic treatment in ICU-patients was the continuous renal replacement therapy (CRRT), in particular continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD) and continuous venovenous hemodiafiltration (CVVHDF) modes, in 6, 8 and 2 patients respectively. In NICU-patients we used the high-efficiency daily hemodialysis (HHD).

Our protocol provided for all patients a peripheral vascular access by a double-lumen catheter inserted in the femoral vein, the use of bicarbonate buffer and polyacrylonitryle filters (PAN AN69). Potassium and Calcium levels in the dialysate varied according to patient's needs.

In CVVH mode the mean session length was 12 hrs, with QB = 100 mL/min and QF = 2000 mL/min; in CVVHD mode the mean session length was 24 hrs, with QB = 100 mL/min and QD = 1500 mL/min; in CVVHDF mode the mean session length was 24 hrs, with QB = 100 mL/min, QD = 1500 mL/min and QF = 2000 mL/min. In HHD treatment, session length was 90–120 min with QB = 300–350 mL/min and QD = 500 mL/min. During hospitalization all patients received medical therapy (dehydration and electrolyte imbalance correction, forced diuresis and urine alkalinization).

Results are expressed by mean values and standard deviation.

RESULTS

Patients' clinical data are shown in Table 1, while biochemical data, dialytic treatment features and patients' outcomes are summarized in Table 2.

Table 2. Biochemical Data Before Starting Dialytic Treatment and RML Clinical Course

Pz N°	CPK (U/L)	K^+ (mEq/L)	SCr (mg/dL)	HD (n°)	CRRT (Days)	Outcome
1	8100	5.5	6	7	–	R^1
2	7400	5	5.8	6	–	R
3	16500	6.8	5.5	6	–	R
4	12500	5.8	5.2	5	–	R
5	9000	5.2	5.5	5	–	R
6	36000	7.1	6.5	8	–	D^2
7	6300	4.8	5.9	7	–	R
8	13500	7.2	6	7	–	R
9	4800	5	6.2	5	–	R
10	23500	6.1	6.3	7	–	R
11	19400	4.7	5.9	8	–	R
12	903	3.5	3.6	–	2	D
13	12500	6.7	11.5	–	18	R
14	3026	6.4	12	–	3	R
15	485	5.5	2.5	–	2	D
16	7250	5	5.4	–	2	D
17	5064	5.3	1.9	–	2	D
18	3641	4	4.4	–	7+2	R
19	603	5.7	10.6	–	12	R
20	856	6.3	6.7	–	2	D
21	889	5.1	1.5	–	9	D
22	579	2.9	1.7	–	8	R
23	998	4.8	2.8	–	2	R
24	9570	5.2	1.5	–	1	R
25	530	4.3	8.4	–	1	R
26	871	5.8	12.2	–	3	D
27	353	4.2	2.8	–	12	D

¹R: Recovery;

²D: Death.

In 16 ICU-patients 81,3% were males (13/16 patients) and 18,7% were females (3/16 patients) and in 11 NICU-patients 63% were males (7/11) and 36,4% were females (4/11).

The mean age in the former group was 64 ± 10 yrs, while in the latter was 36 ± 16 yrs. The causes of RML were different in the two groups. In particular in ICU-patients we found the following causes: 8 patients were suffering from MODS and SIRS (4 cardiogenic shock, 2 acute liver failure, 2 acute respiratory failure), while 8 patients didn't show a SIRS (NSIRS-patients: 3 acute liver failure, 3 cardiogenic shock, 1 chronic respiratory failure, 1 ictus cerebri). In NICU-patients, instead, we found: heroin overdose (6 patients), lipid-lowering drug treatment (3 patients), excessive muscular activity (1 patient) and repetitive seizures (1 patient).

Before starting dialytic procedures ICU-patients had CPK plasma levels of 2615 ± 3586, K+ was 5.10 ± 1.08 and sCr was 5.69 ± 4.06, while NICU-patient had CPK = 14273 ± 9266, K+ = 5,75 ± 0.92 and sCr = 5,9 ± 0.4. The whole CRRT treatment length was on the average 5.5 ± 4.3 days and the mean HHD treatment length was 6.5 ± 1 days. In ICU-patients CPK levels declined to normal values within about 16 days on the average in surviving patients and decreased to half the starting values in all patients after 48 hrs of CRRT treatment. In NICU-patients CPK values declined to normal values within about 2–3 weeks. In all patients muscular function recovery and clinical condition improvement did not run together with renal function recovery and biochemical RML hallmark decrease. In ICU-patients 50% (8/16 patients) survived and recovered from rhabdomyolytic syndrome and got back to a good renal and muscular function, while the remaining 50% attained a renal function improvement anyway but died of serious pathologies subtended to MODS. On the contrary, all NICU-patients (not suffering from MODS) survived except one, who died of septic complications (RML due to heroin overdose), and fully recovered a good renal and muscular function. We considered a patient recovered when sCr levels decreased under 1.5 mg/dL and the patient was able to carry out the basic activity of everyday life.

DISCUSSION

RML is a clinical syndrome resulting from skeletal muscle injury and disruption of the sarcolemma, with release of components usually held within the muscular cells into the plasma [[8]]. RML may result from several different causes, either traumatic or non-traumatic. The formers include surgical intervention, crush-syndrome, vigorous exercise, seizures and battering [9-10]. The latter include inadequate blood perfusion, metabolic and electrolytic disturbances, septic syndrome, inflammatory myopathies, hereditary enzyme deficiencies, direct injury by myotoxic drugs, narcotics, toxins and poisons [11-14]. Any pathology, which may in some way interfere with cellular metabolism leading to disorder and insufficient energy production, may result in RML. This happens because of the inhibition of cellular membrane ATP-dependent transporters with intracellular accumulation of Na⁺ and Ca⁺⁺ and abnormal activation of intracellular enzymes, thus leading to cellular necrosis and release of CPK, LDH, AST, uric acid, potassium, phosphates and other intracellular compounds [[15]].

In our series we found RML causes in ICU-patients different from NICU-patients ones. Patients in the first group were older, with a mean age of 64 ± 10 yrs, and were suffering from MODS and typical elderly diseases, such as cardiac and respiratory chronic failure, except from 3 patients with acute liver failure resulting from poisoning, who were relatively younger. In NICU-patients, instead, the mean age was 36 ± 16 yrs and the causes of RML were narcotic drugs abuse, repetitive seizures and vigorous exercise, more frequently observed in young people. In three relatively older NICU-patients RML was due to lipid-lowering drugs assumption.

RML peculiar laboratory parameters are the following. increased CPK plasma levels (peak value occurs generally within 72 hrs after muscular damage), hyperkalemia, hyper or hypocalcemia, hyperphosphatemia and increased AST plasma levels. Then an alteration in renal function indexes, particularly serum creatinine increase, occurs. In our series the initial CPK levels increase was observed earlier in ICU-patients because they were already carefully monitored, as usual in ICU departments, before the rhabdomyolytic syndrome development. For this reason CPK levels estimated before starting the dialytic treatment were lower than those in NICU-patients, who came under our observation when muscular injury was in an advanced phase. Before starting the dialytic treatment, in ICU-patients CPK plasma level was 2615 ± 3586, while K⁺ was 5.10 ± 1.08 and sCr was 5.69 ± 4.06. In NICU-patients, on the other hand, CPK was 14273 ± 9266, while K⁺ was 5,75 ± 0.92 and sCr was 5,9 ± 0.4.

If not timely diagnosed and treated, the rhabdomyolytic syndrome may result in several life-threatening complications, such as cardiac arrest, compartment syndrome, DIC and ARF [[16]]. Previous literature has described an 8–20% incidence of ARF in rhabdomyolysis [[2]] and a 16.4% incidence of ARF and RML in ICU departments [[4]]. Several damage factors may contribute to ARF onset: direct toxicity of myoglobin degradation products, tubular obstruction due to protein, uric acid crystals and myoglobin casts, and reduction in renal blood flow as a result of renal vasoconstriction [[17]].

The main goal of RML therapy is to prevent acute renal failure, from which all the complications previously described may result. To prevent ARF onset, hypovolemia correction, adequate diuresis induction and urine alkalinization may be useful [[18]]. Dialytic treatment remains necessary to correct biochemical abnormalities, remove myoglobin from the plasma, and protect the kidney against metabolic acidosis and intratubular myoglobin precipitates. Early dialysis may avoid complications and allow a fast renal function recovery with immediate correction of hydroelectrolytic imbalance and metabolic acidosis. Furthermore, the use of high-permeability membranes, like PAN in our study, results in a better myoglobin removal (pathogenetic therapy). The continuous renal replacement therapy is preferable in ICU-patients suffering from multiorgan dysfunction because it answers better to patients clinical needs (severe hemodynamic and respiratory conditions) [[19]], even though the dialytic adequacy is comparable to the intermittent dialysis one. Instead, in patients suffering from RML only, the high-efficiency daily hemodialysis is perfectly adequate. We treated ICU-patients by CRRT: in particular 6 patients received CVVH, 8 patients received CVVHD and 2 patients received CVVHDF. The mean duration of the whole treatment was 3, 6 and 10 days respectively. NICU-patients on the other hand received high-efficiency daily hemodialysis with a session length of 3–4 hrs and a mean treatment duration of 6 days on the whole. Muscular damage and acute renal failure prognosis is generally good but it's not the same in the case of complication developed before starting dialytic therapy (our previous study) [[20]] and for MODS pathologies in critically ill patients. In fact in such patients the mortality rate remains high, in spite of the improvement of renal function by dialytic treatment and of the resolution of the rhabdomyolytic syndrome, which is possible but much more difficult with respect to NICU-patients. In our series, ICU-patients mortality rate was 50% (8/16 patients) in spite of the good recovery of renal function and the biochemical RML indexes improvement. In NICU-patients, instead, only one patient died for septic complications (he was a heroin-addict and suffered from overdose syndrome).

Generally speaking, however, in patients who overcome the critical phase the improvement in renal function and in biochemical indexes is not correlated to the improvement in muscular function, which in fact requires a longer time for fully recovering.

CONCLUSIONS

Early diagnosis of the rhabdomyolytic syndrome is very important. In fact, using high-permeability membranes and convective techniques, early dialytic treatment of RML allows not only to avoid life-threatening complications (first of all the acute renal failure) but moreover it's a pathogenetic treatment because it removes great amount of myoglobin from the plasma. Beside this, continuous renal replacement therapy allows a successful management of critically ill patients with severe hemodynamic conditions. Renal and muscular function prognosis is good but it depends on a large extent on the rapidity in starting treatment and on patient's clinical conditions. Anyway, early treatment is an essential factor for a good recovery of renal function, either in ICU-patients or in NICU-patients. Nevertheless, the final outcome may be very different between these two kinds of patients, with a higher mortality rate in ICU-patients suffering from MODS.