Michael S. Clemens

Rhabdomyolysis among critically ill combat casualties: Associations with acute kidney injury and mortality.

BACKGROUND Rhabdomyolysis has been associated with poor outcomes in patients with traumatic injury, especially in the setting of acute kidney injury (AKI). However, rhabdomyolysis has not been systematically examined in a large cohort of combat casualties injured in the wars in Iraq and Afghanistan. METHODS We conducted a retrospective study of casualties injured during combat operations in Iraq and Afghanistan who were initially admitted to the intensive care unit from February 1, 2002, to February 1, 2011. Information on age, sex, Abbreviated Injury Scale (AIS) score, Injury Severity Score (ISS), mechanism of injury, shock index, creatine kinase, and serum creatinine were collected. These variables were examined via multivariate logistic and Cox regression analyses to determine factors independently associated with rhabdomyolysis, AKI, and death. RESULTS Of 6,011 admissions identified, a total of 2,109 patients met inclusion criteria and were included for analysis. Rhabdomyolysis, defined as creatine kinase greater than 5,000 U/L, was present in 656 subjects (31.1%). Risk factors for rhabdomyolysis identified on multivariable analysis included injuries to the abdomen and extremities, increased ISS, male sex, explosive mechanism of injury, and shock index greater than 0.9. After adjustment, patients with rhabdomyolysis had a greater than twofold increase in the odds of AKI. In the analysis for mortality, rhabdomyolysis was significantly associated with death until AKI was added, at which point it lost statistical significance. CONCLUSION We found that rhabdomyolysis is associated with the development of AKI in combat casualties. While rhabdomyolysis was strongly associated with mortality on the univariate model and in conjunction with both ISS and age, it was not associated with mortality after the inclusion of AKI. This suggests that the effect of rhabdomyolysis on mortality may be mediated by AKI. LEVEL OF EVIDENCE Prognostic and epidemiologic study, level III.

Reciprocal Risk of Acute Kidney Injury and Acute Respiratory Distress Syndrome in Critically Ill Burn Patients

Objective:To evaluate the association between acute respiratory distress syndrome and acute kidney injury with respect to their contributions to mortality in critically ill patients. Design:Retrospective analysis of consecutive adult burn patients requiring mechanical ventilation. Setting:A 16-bed burn ICU at tertiary military teaching hospital. Patients:Adult patients more than 18 years old requiring mechanical ventilation during their initial admission to our burn ICU from January 1, 2003, to December 31, 2011. Interventions:None. Measurements and Main Results:A total 830 patients were included, of whom 48.2% had acute kidney injury (n = 400). These patients had a 73% increased risk of developing acute respiratory distress syndrome after controlling for age, gender, total body surface area burned, and inhalation injury (hazard ratio, 1.73; 95% CI, 1.18–2.54; p = 0.005). In a reciprocal multivariate analysis, acute respiratory distress syndrome (n = 299; 36%) demonstrated a strong trend toward developing acute kidney injury (hazard ratio, 1.39; 95% CI, 0.99–1.95; p = 0.05). There was a 24% overall in-hospital mortality (n = 198). After adjusting for the aforementioned confounders, both acute kidney injury (hazard ratio, 3.73; 95% CI, 2.39–5.82; p < 0.001) and acute respiratory distress syndrome (hazard ratio, 2.16; 95% CI, 1.58–2.94; p < 0.001) significantly contributed to mortality. Age, total body surface area burned, and inhalation injury were also significantly associated with increased mortality. Conclusions:Acute kidney injury increases the risk of acute respiratory distress syndrome in mechanically ventilated burn patients, whereas acute respiratory distress syndrome similarly demonstrates a strong trend toward the development of acute kidney injury. Acute kidney injury and acute respiratory distress syndrome are both independent risks for subsequent death. Future research should look at this interplay for possible early interventions.

Mechanism of Stent Failure in a Patient with Fibromuscular Dysplasia following Renal Artery Stenting

Endovascular techniques used in the management of renal artery stenosis (RAS) have unique complications, to include stent facture, thrombosis, aneurysm formation, migration, and in-stent restenosis. Described here is an unusual complication of renal artery obstruction and recurrent hypertension without progressive loss of renal function, secondary to intermittent arterial kinking with respiratory and cardiac motion in a patient with fibromuscular dysplasia. This mechanical complication has implication not only in successful endovascular treatment of RAS, but raises questions regarding the alterations in dynamic motion with the cardio-respiratory cycle in stented visceral arteries in other vascular pathologies requiring renal artery stenting (i.e., juxtarenal or pararenal aortic aneurysms).

A Diagnostic Evolution: Surgical Experience with Popliteal Artery Entrapment Syndrome at a Military Tertiary Referral Center

BACKGROUND Popliteal artery entrapment syndrome (PAES) is an increasingly encountered disorder that typically presents as claudication in young and active individuals. However, despite the increased recognition, accurate preoperative diagnosis can be difficult. The objective of this study was to describe the surgical assessment and outcomes of patients treated for PAES. METHODS Retrospective case series of all patients managed surgically for a diagnosis of PAES at the San Antonio Military Medical Center from 2005 to 2013. RESULTS Over 8 years, PAES was surgically treated in 25 consecutive limbs of 15 patients (mean age, 35; range, 21-49) in a military tertiary medical center. Type III was the most common variant (n = 13, 52%), followed by type VI (n = 7, 28%). Most patients presented with class I or II ischemia (88%), with anterolateral symptoms (56%), and were referred by orthopedics (66%). Diagnostic work-up included stress ankle-brachial indices, magnetic resonance imaging (MRI) and provocative angiography. Sixty-three percent of limbs with negative MRI demonstrated findings consistent with either type III or V PAES. Tendon release was used in those with types III and V, whereas liberal myectomy was used in those with types I, II, or VI. Two patients required revascularization. At a median follow-up of 126 days (range, 25 days-7 years), 83% of patients with type III demonstrated partial resolution of symptoms. Only 27% of patients without an identifiable muscle slip had clinical improvement. CONCLUSIONS Despite modern imaging, open surgical exploration remains the definitive diagnostic modality for PAES. Patients with a muscular or tendinous slip identified intraoperatively have the best clinical outcomes. Those with no identifiable muscle slip (functional entrapment) are less likely to demonstrate clinical improvement. Further evaluation on outcomes in the management in PAES is warranted.

Validation of the Short Musculoskeletal Function Assessment in patients with battlefield-related extremity vascular injuries

OBJECTIVE Vascular extremity injuries can be a significant burden on a patients long-term quality of life. Currently, no limb-specific surveys have been used to quantify the relation between injury pattern and the resultant physical or psychological impact. The objective of this study was to validate the use of the Short Musculoskeletal Function Assessment (SMFA) in the setting of extremity vascular injury. METHODS The Joint Theater Trauma Registry was queried and filtered for U.S. troops with an extremity vascular injury isolated to a single limb. Injury and management data were obtained, and the SMFA was administered after patient contact and consent. Validity was analyzed by characterization of SMFA score distribution, correlation with 36-Item Short Form Health Survey (SF-36) scores, and assessment of its discriminative capability to external measures of injury severity (ie, Injury Severity Score [ISS], Mangled Extremity Severity Score [MESS], and Medicare Part A disability qualification). RESULTS At mean follow-up of 5 years, 164 patients (median age, 25 years; interquartile range, 22-31 years) completed both surveys. The overall SMFA Dysfunction Index was 24.8 ± 15.2 (range, 0-78; skewness, 0.60; floor/ceiling effect, 0%-1.2%; and nonresponse, 0%), and the overall Bother Index was 29.4 ± 20.2 (range, 0-96; skewness, 0.58; floor/ceiling effect, 0%-4.3%; and nonresponse, 0.6%). SF-36 physical component summary scores correlated inversely with the Dysfunction Index (r = -0.64; P < .01), whereas mental component summary scores correlated inversely with the Bother Index (r = -0.59; P < .01). No difference was found in reported scores between those considered severely injured (ISS > 15) and those not severely injured (ISS ≤ 15). However, those with mangled extremities (MESS ≥ 7) reported higher Dysfunction and Bother indices than those with lower scores (P < .05). In addition, patients considered disabled (per Medicare Part A qualifications) reported higher Dysfunction and Bother indices compared with those not considered disabled (P < .05). CONCLUSIONS Use of the SMFA is validated in those with extremity vascular injuries, and it should be considered an adjunctive tool in evaluating long-term patient outcomes.

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia

BackgroundThe critically ill can have persistent dysglycemia during the “subacute” recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial.MethodsEight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation.ResultsSubcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, “rebound hyperglycemia” was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes.ConclusionsSubcutaneous regular insulin consistently lowered mean glucose concentrations and glucose variability; its linear dose-response curve rendered the preparation better suited for a sliding-scale protocol. The longer duration of action of subcutaneous regular insulin resulted in better glycemic-control metrics for patients who were continuously postprandial. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units; if present, their clinical effects should be evaluated.

Comparison of Subcutaneous Regular Insulin and Lispro Insulin in Diabetics Receiving Continuous Nutrition A Numerical Study

Background: Optimal management of non–critically ill patients with diabetes maintained on continuous enteral feeding (CEN) is poorly defined. Subcutaneous (SQ) lispro and SQ regular insulin were compared in a simulated type 1 and type 2 diabetic patient receiving CEN. Method: A glucose-insulin feedback mathematical model was employed to simulate type 1 and type 2 diabetic patients on CEN. Each patient received 25 SQ injections of regular insulin or insulin lispro, ranging from 0-6 U. Primary endpoints were the change in mean glucose concentration (MGC) and change in glucose variability (GV); hypoglycemic episodes were also reported. The model was first validated against patient data. Results: Both SQ insulin preparations linearly decreased MGC, however, SQ regular insulin decreased GV whereas SQ lispro tended to increase GV. Hourly glucose concentration measurements were needed to capture the increase in GV. In the type 2 diabetic patient, “rebound hyperglycemia” occurred after SQ lispro was rapidly metabolized. Although neither SQ insulin preparation caused hypoglycemia, SQ lispro significantly lowered MGC compared to SQ regular insulin. Thus, it may be more likely to cause hypoglycemia. Analyses of the detailed glucose concentration versus time data suggest that the inferior performance of lispro resulted from its shorter duration of action. Finally, the effects of both insulin preparations persisted beyond their duration of actions in the type 2 diabetic patient. Conclusions: Subcutaneous regular insulin may be the short-acting insulin preparation of choice for this subset of diabetic patients. Clinical trial is required before a definitive recommendation can be made.

A technique for endograft relining of a type IV endoleak using a surgeon-modified internal gate.

Type IV endoleaks represent a rare etiology of late endograft failure; however, depending on the location, they can be extremely challenging to repair with endovascular solutions. We present a method of endograft relining that preserves antegrade limb perfusion, avoids extra-anatomic reconstructions, and ensures complete endograft exclusion.

Magnetic resonance imaging: occult popliteal artery entrapment syndrome in a young soldier.

BACKGROUND Popliteal artery entrapment syndrome (PAES) is frequently misdiagnosed because of symptom overlap with other conditions and lack of a definitive diagnostic modality. The incidence is widely variable, although it should be considered in all patients under 50 years with symptoms of lower extremity claudication. Long-term sequelae of PAES include critical limb ischemia, arterial occlusion, and aneurysm formation caused by repetitive external compression. METHODS We review the case of a 27-year-old soldier originally treated for exertional compartment syndrome with fasciotomies without relief of symptoms. Magnetic resonance imaging (MRI) failed to demonstrate an aberrant slip of the gastrocnemius muscle, which was ultimately found and released on surgical exploration. RESULTS Surgical exploration and release of an aberrant band of gastrocnemius muscle through a medial approach resulted in significant relief of symptoms and improvement of walking distance. CONCLUSIONS Healthy athletes without peripheral vascular disease and symptomatic calf and foot claudication should have an early referral to vascular surgery. The risk of false-negative MRI warrants further investigation into provocative, noninvasive imaging modalities to properly classify PAES. This report reviews the literature to discuss the diagnostic challenges, natural history of disease, and surgical interventions for PAES.

Extracorporeal Filtration of Potassium in a Swine Model of Bilateral Hindlimb Ischemia–Reperfusion Injury With Severe Acute Hyperkalemia

Introduction Options for the treatment of hyperkalemia in the pre-hospital setting are limited, particularly in the context of natural disaster or during combat operations. Contemporary interventions require extensive resources and technical expertise. Here we examined the potential for a simple, field deployable bridge-dialysis as a countermeasure for acute hyperkalemia induced by prolonged ischemia-reperfusion. Methods Twenty female swine were randomized into two experimental groups undergoing a 2-hour bilateral hindlimb ischemia-reperfusion injury. Subsequent to injury, hemoperfusion was performed in the presence (Column) and absence (Sham Control) of a high-affinity potassium-binding column (CytoSorbents, Monmouth Junction, NJ, USA). Serial blood gas and chemistries were sampled. Primary endpoint was changed in serum potassium concentrations post-injury and filtration. Results Serum potassium was significantly elevated following ischemia-reperfusion injury in both groups (149% (12) and 150% (22), p < 0.05 vs respective baseline values). There were no differences observed between groups in respect to physiologic parameters; mean arterial pressure, heart rate, systemic vascular resistance, cardiac output, or central venous oxygenation. Filtration resulted in a significant relative decrease in potassium compared with controls after the first hour as determined by repeated measures two-way ANOVA (p < 0.0001) which continued through end of the study. Significant thrombocytopenia was observed in animals undergoing filtration with a mean reduction in platelets measured at T = 480 minutes (168 × 103μL, p < 0.0001 vs baseline). Conclusions We demonstrate that serum potassium can be filtered via hemoperfusion utilizing a simple extracorporeal potassium-binding platform, though evolution of this technology will be required to achieve meaningful reduction of potassium in clinically significant hyperkalemia after trauma.