Abstract
Context:
Exertional rhabdomyolysis (ER) is a medical condition in which excessive and unaccustomed physical activity results in skeletal muscle damage in otherwise healthy individuals.
Objective:
To assess the overall outcomes of patients who presented to the emergency department with ER.
Methods:
This retrospective study was conducted across 4 hospitals. The study included nonpregnant adults with no history of renal function impairment or myopathy disorder who had a diagnosis of ER in the emergency department setting. Medical records were reviewed for patient demographics, length of stay, complications, mechanism(s) of injury involved, impact of nutritional supplements, spectrum of creatine kinase (CK) responses, prevalence of hospital readmissions, and overall mortality.
Results:
Of the 800 rhabdomyolysis cases identified during the 24-month study period, 41 were included in the study. The mean age was 29 years, and the patients were predominantly male (33 [80.5%]) and white (25 [61%]). The median length of stay was 2 days, and it correlated significantly with initial and peak CK levels (R=0.45, P=.004, and R=0.52, P<.001, respectively). Median initial and peak CK were noted to be 16,888 (range, 342-194,403) U/L and 18,534 (range, 342-287,565) U/L, respectively. Median discharge CK was 5287 (range, 10-61,617) U/L. The most commonly cited mechanism of injury was weight lifting (16 [39%]). In terms of overall outcomes, transient kidney injury was noted in 3 cases (7.4%), and no mortality was recorded during the admission or at 12 months of follow-up. Compartment syndrome or severe electrolyte abnormalities were not observed. There were only 2 uncomplicated readmissions (4.8%) due to high-intensity interval training.
Conclusion:
Hospitalized patients with ER without a history of renal impairment tend to have relatively low risks of complications and readmission.
Exertional rhabdomyolysis (ER) is a condition in which excessive and unaccustomed physical activity results in skeletal muscle damage in otherwise healthy persons. Patients typically present with muscle pain, weakness, and decreased range of motion, largely localized to the muscle groups that were involved in the activity.
1 Rhabdomyolysis from all causes accounts for 7% to 10% of all cases of acute renal failure in the United States. Mortality from rhabdomyolysis could be as high as 8%.
2 Complications are rare but can range from mild acute kidney injury (AKI) to renal failure if left untreated. Life-threatening electrolyte abnormalities, compartment syndrome, and disseminated intravascular coagulopathy are possible but rare complications. Risks that may lead to complications include the nature of the athletic activity, previous rhabdomyolysis, nutritional supplements, and performance-enhancing agents, drug or alcohol abuse, genetic predisposition (sickle cell trait), preexisting metabolic myopathy, certain medications (eg, statins, antidepressants, nonsteroidal anti-inflammatory drugs, antipsychotics, sedative hypnotics, antiseizure, antihistamines), heat stress, dehydration, shock, acidosis, and preexisting illness.
2
Various recreational activities frequently produce large increases in circulating creatine kinase (CK) without consequences.
3 Treatment is usually supportive, correcting for electrolyte/metabolic abnormalities and hypovolemia. Some studies suggest alkalization of urine after adequate fluid resuscitation. Diuretics can be used to increase urine output. For patients with persistent acute renal failure, renal replacement therapy is indicated.
2 Oral hydration and outpatient observation may suffice for a stable patient with a CK level of 20,000 to 50,000 U/L (and possibly higher), normal creatinine level, and good urine flow.
3
The true incidence of ER in the general population is hard to determine because most patients tend to self-treat. The patients who eventually present to emergency departments are often admitted for intravenous hydration. Whether or not all patients with ER require hospitalization is a topic worth exploring, especially as health care facilities in the United States strive to improve quality of care, enhance patient experience, and lower health care costs. We therefore aimed to assess the overall outcomes of patients who presented to the emergency department with ER.
The study received approval from the institutional review board at the Henry Ford Hospital in Detroit, Michigan. Electronic patient records were reviewed between January 1, 2014, and January 1, 2016, in 4 hospitals within the system (1 tertiary care hospital/level 1 trauma center and 3 suburban community hospitals). The targeted study population included all adult patients (n=800) who presented to the 4 emergency departments for rhabdomyolysis with
International Statistical Classification of Diseases and Related Health Problems, Ninth Revision code 728.88. Clinically relevant rhabdomyolysis was defined as an acute onset of diffuse or focal muscle pain, swelling, or weakness lasting fewer than 7 days, with serum CK elevation or a urine dipstick positive for blood but absent of red blood cells on urine microscopy.
4
All nonpregnant patients older than 18 years were eligible for study inclusion. To limit potential bias and confounding factors, patients were excluded from the study if any of the following criteria were met: prior renal impairment, statin use, history of metabolic myopathy, rhabdomyolysis from toxin ingestion, trauma, or exertional heat illness.
Medical records were reviewed for patient demographics, hospital length of stay, complications (AKI, compartment syndrome, severe electrolyte abnormalities), the mechanism(s) of injury, preexisting comorbidities, impact of nutritional supplements, amount of intravenous fluids in relation to CK decrease, prevalence of hospital readmissions, and overall mortality.
Normally distributed continuous variables are expressed as mean (SD); nonnormally distributed continuous variables are presented as median (range), and categorical data are presented as No. (%). Univariate 2-sample t tests for continuous variables with normal distributions, Wilcoxon 2-group tests for continuous variables with nonnormal distributions, and Fisher exact tests to compare categorical variables were carried out. The correlation between 2 continuous variables was examined using Spearman correlation coefficient. These nonparametric tests were used because of the small sample size and nonnormal distributions. Statistical significance was set at P<.05. All analyses were performed using SAS for Windows 9.4 (SAS Institute Inc).
Of the 800 patient records reviewed, 41 met the inclusion criteria. The majority of the patients (n=737) were excluded because of a nonexertional mechanism of rhabdomyolysis (
Figure). Among the 41 patients who qualified for the study, the mean (SD) age was 29.1 (7.8) years (
Table 1). The patients were predominantly male (33 [80.5%]) and white (25 [61%]). Chronic comorbidities were noted in 8 patients (19.5%); 3 (1.2%) had hypertension, 1 (0.4%) had lupus, 1 (0.4%) had asthma, and 3 (1.2%) had a mood disorder. Laboratory values are presented in
Table 2.
Weight lifting was the most frequent mechanism of injury for rhabdomyolysis in 16 of the cases (39%) (
Table 3). In 21 patients who had liver enzymes checked on admission, median aspartate aminotransferase level was 265 (range, 48-2176) U/L and median alanine aminotransferase level was 132 (range, 45-614) U/L. Mean (SD) creatine and blood urea nitrogen levels were 1.0 (0.4) mg/dL and 13.4 (5.6) mg/dL, respectively. Median initial and peak CK levels were noted to be 16,888 (range, 342-194,403) U/L and 18,534 (342-287,565) U/L, respectively. Median discharge CK level was 5287 (range, 10-61,617) U/L.
Initial and peak CK levels were significantly and positively correlated with length of stay (
R=0.45,
P=.004, and
R=0.52;
P<.001, respectively). There was no evidence of a statistically significant correlation between length of stay and discharge CK level or 7-day follow-up. Additionally, no evidence of a statistically significant correlation was found between creatinine levels and CK initial, peak, discharge, and 7-day follow-up levels (
Table 4). Change in CK and intravenous fluid bolus was also not significant (
P=.249).
One patient was discharged from the emergency department without being admitted to the hospital, and 3 patients were discharged within 24 hours. The determining factor for early discharge was lower CK levels (range, 342-1247 U/L).
No evidence of a statistically significant difference (P=.919) was found in initial CK level when comparing patients taking supplements (n=15) with patients not taking supplements (n=9) and with patients with unknown supplement intake (n=17).
In terms of overall outcomes, transient mild kidney injury was noted in 3 patients (7.3%), and no mortality was recorded during the admission or follow-up. Compartment syndrome or severe electrolyte abnormalities were also not observed. Two patients (4.8%) had uncomplicated readmissions because of high-intensity interval training in 12 months of follow-up. There were too few women (n=8) to compare outcomes of men with those of women.
We assessed the overall outcomes and spectrum of CK responses in the ER population. The population sample was relatively young, with the majority of patients lacking any comorbidities. The most common mechanism of injury was weight lifting. The high-force eccentric contractions involved in weight lifting tend to produce a large strain on muscle fibers, causing greater damage than forces during activities of endurance. This type of isolated, high-force exercise has been shown to generate both larger (>5000 U/L) and delayed (4-5 days after exercise) peak circulating CK.
3 However, there was no statistically significant correlation between type of mechanism of injury and CK elevation in this sample, which could partly result from the small sample size. Furthermore, reported hospital CK levels may not represent a true peak level, as onset of symptoms, type of exertional exercise, and, more importantly, patients’ physical preparedness varies. These factors are also difficult to ascertain retrospectively.
Individual physician preference may play a role regarding their level of comfort in dealing with the admission and discharge of patients with ER, which may be partly because of the widely different expert opinions regarding CK levels and discharge. Several sources recommend hospitalization for rhabdomyolysis until CK level drops to less than 1000 U/L.
5,6 Other experts have argued that discharge at higher CK thresholds of 20,000 to 50,000 U/L can be safely achieved in the emergency department.
3,5
The majority of the patients in the current study were admitted to the hospital, with early discharge (within 24 hours) in 4 patients with much lower admission CK levels (342-1247 U/L). Creatine kinase levels were significantly positively correlated with length of stay. Oh et al
7 examined 30 patients with ER and noted that higher peak CK levels predicted longer lengths of stay. Based on this correlation, further investigation may be needed to assess whether we are determining the need for admission or making decisions about the length of hospitalization based solely on CK elevation. The current laboratory diagnostic guidelines for exertional rhabdomyolysis, particularly with regard to CK levels, have a specificity that is too low for the diagnosis of clinical ER. The proposed guideline for ER diagnosis is a serum CK level greater than 50× the upper limits of normal (corresponding to CK >12,000 U/L).
8 Kenney et al
9 investigated the spectrum of CK responses in 499 military recruits undergoing basic training. The serum CK levels ranged widely (34-35,056 U/L), and none of the participants developed clinical ER. Thus, a more stringent CK elevation as a diagnostic marker was suggested. Patients with serum CK levels less than 50 times the upper limit of normal, no definite muscle swelling or weakness, no myoglobinuria, and no laboratory evidence of AKI or electrolyte imbalance have most likely expressed a normal physiologic response to exercise and should not be classified as having clinically significant ER.
9 Nevertheless, this guideline may have to be modified for civilians, as their physical endurance differs from military recruits.
The most severe complication and likely main determinant for hospitalization of patients with ER is AKI. Three patients (7.4%) had AKI on admission, signifying a much lower incidence of AKI in ER than in rhabdomyolysis induced by other nephrotoxic cofactors. These patients had no prior renal impairment or supplement or medication use and were discharged without any complications. Overall, no deaths were reported, and the readmission rate was low, with 2 uncomplicated readmissions due to high-intensity interval training.
In accordance with current knowledge, several important factors should be considered when admitting patients with ER. They tend to be younger and generally healthier, with fewer complications than the population in whom rhabdomyolysis develops from other causes. Clarkson et al
10 prospectively evaluated 203 healthy volunteers after exercise and concluded that despite marked CK elevations in some participants, none required treatment for impaired renal function. In a retrospective review of 35 patients with ER, Sinert et al
11 found no incidence of AKI. The mean age of the patients was 24.4 years, and the mean creatine phosphokinase level was 40,471 U/L. However, in 2 retrospective studies on patients who were admitted with rhabdomyolysis from different causes, the incidence of AKI was significant, and the population was older.
12,13
Our study had several limitations. Even though it was conducted in a large health system that serves a diverse patient population, our sample population had little demographic diversity. This factor may limit the generalizability of the results to other clinical settings. Consequently, the sample may have been underpowered to detect meaningful sample subgroup differences that might have been found in a larger study sample. Furthermore, our study included nonrandom presentation of ER patients to the emergency department. There was no control group of patients with ER who did not present to the emergency department, as many patients with ER elect to self-treat. The study design is subject to selection and information bias and the availability and accuracy of data.
Distinguishing between physiologic ER and clinically significant ER can be difficult. Our investigation was primarily intended to support the importance of additional inquiry into the outcomes of patients with ER. Hence, patients with ER with no history of renal impairment in the absence of the previously identified risk factors tended to have a low risk of complications. This finding combined with findings of past studies can aid physicians when it comes to decision-making in terms of admission and timing of discharge. As our health care systems tend to advocate for low-cost, high-value health care, prospective investigation of early discharge and outpatient management of patients with ER may be useful.
Both authors provided substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; both authors drafted the article or revised it critically for important intellectual content; both authors gave final approval of the version of the article to be published; and both authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.