Pre-existing cardiac disease, troponin I elevation and mortality in patients with severe sepsis and septic shock.
A prospective, observational study was undertaken to determine the frequency of troponin I elevation and the incidence of pre-existing cardiac disease in patients with severe sepsis and septic shock, and to determine their relationship to mortality.
The setting was the surgical intensive care unit of a tertiary care medical centre. Sixty-six consecutive patients admitted with severe sepsis or septic shock requiring pulmonary artery catheterisation for haemodynamic monitoring were studied. Measurement of troponin I was done at the time of pulmonary artery catheterisation and every six to eight hours if there was ongoing tachycardia, hypotension or arrhythmias requiring treatment. Preexisting cardiac disease was determined from the patient andlor family members as well as from the medical record. Significant cardiac history was defined as prior myocardial infarction; abnormal treadmill report, nuclear medicine study or coronary angiogram; history of congestive heart failure or arrhythmia requiring treatment.
Forty-two patients (64%) had elevated troponin I at study entrance and 23 patients (35%) had pre-existing cardiac disease. History of cardiac disease was associated with reduced cardiac index and oxygen delivery, and a nearly three fold increase in mortality (44% vs. 16%, P=0.03), irrespective of elevated troponin I levels. Troponin I elevation alone was not associated with increased mortality.
We conclude that pre-existing cardiac disease and elevated troponin I are commonly found in surgical patients with severe sepsis and septic shock. In our study, pre-existing cardiac disease, and not troponin I elevation, was associated with increased mortality.
Key Words: troponin 1, sepsis, septic shock, cardiac disease, myocardial dysfunction, pulmonary artery catheter, mortality
Severe sepsis and septic shock afflict an estimated 750,000 people in the United States each year and together are the leading cause of death in the intensive care unit (1). Myocardial dysfunction in the setting of severe sepsis and septic shock is well documented. Decreased systolic function, reversible ventricular dilation and reduced responsiveness to fluid resuscitation and catecholamines characterise this dysfunction (2). Cytokines such as tumour necrosis factor- [alpha] and interleukin-1[beta] may act as circulating myocardial depressants, given that global myocardial perfusion has been shown to be normal or increased (3-6).
Serum assays for troponin are highly sensitive and specific markers for myocardial cell injury. The American College of Cardiology, the American Heart Association and the European Society of Cardiology have accepted troponin measurement in serum as the standard biomarker for the diagnosis of acute myocardial infarction and for diagnosis, risk stratification and management of acute coronary syndromes (7-8).
Elevations of troponin I have been predictive of increased mortality in patients with acute coronary syndrome (9,10) and even moderate elevations have been associated with increased morbidity and mortality in surgical intensive care unit (SICU) patients (11). Multiple smaller studies have characterised the incidence of troponin I elevation in patients with critical illness or sepsis (12,18). Elevated troponin I has been reported in 43 to 85% of patients, depending on the threshold value utilised to define an elevated level (19). In this context, these investigations arrived at the collective conclusion that elevations of troponin I correlated with depressed left ventricular function and increased mortality. These studies were conducted in general or medical intensive care units and consisted of small groups of patients.
We conducted the present analysis of myocardial injury in patients with severe sepsis or septic shock in a single institutional, tertiary care referral centre, to quantitate the incidence of pre-existing cardiac disease and troponin I elevations in patients admitted to an SICU. This was undertaken to further determine the potential impact these parameters had on mortality in surgical patients with severe sepsis and septic shock.
MATERIALS AND METHODS
Patients with severe sepsis and septic shock admitted to the SICU requiring placement of a pulmonary artery catheter were prospectively observed for the duration of their hospital course.
Indications for pulmonary artery catheter placement included: persistent tachycardia (heart rate >100 /min), hypotension (systolic blood pressure <90 mmHg), urinary output <0.5 ml/kg/h after fluid replacement, worsening oxygenation ([P.sub.a][O.sub.2]/Fi[O.sub.2] <150 mmHg) or deteriorating renal function (serum creatinine increase by >20% from baseline).
Severe sepsis was defined as a documented infection accompanied by the systemic inflammatory response syndrome and evidence of organ dysfunction. Septic shock was defined as severe sepsis accompanied by persistent hypotension (systolic blood pressure <90 mmHg or decrease >40 mmHg for at least one hour) requiring vasopressors after adequate fluid resuscitation, as defined by Bone et al (20).
In order to prevent confounding of the differentiation between acute and chronic cardiac disease, abnormal cardiac studies obtained either on admission to the SICU or subsequent to admission did not constitute criteria for pre-existing, or prior, cardiac disease. Pre-existing history of cardiac disease was defined as either an abnormal treadmill report (any exercise-induced ischaemia), nuclear medicine study (any chemically induced ischaemia or levidence of reversible or nonreversible ischaemia), or coronary angiogram (ejection fraction <40%, evidence of prior infarction, or coronary artery stenosis or occlusion); prior myocardial infarction; history of congestive heart failure; or arrhythmia requiring treatment, preceding the current hospital admission.
Prior to study inception we selected a history of an abnormal echocardiogram (ejection fraction <40%, or any degree of wall motion abnormality), as one of the screening criteria to identify potential subjects, in order to capture all patients with a history of pre-existing cardiac disease for this study. In all instances the echocardiograms that had been obtained prior to the current hospital admission were done in patients with a history of ischaemic coronary artery disease (one patient), atrial fibrillation requiring pharmacologic therapy (two patients), or congestive heart failure (two patients). Therefore, prior history of an abnormal echocardiogram did not add to the identification of patients with a pre-existing history of cardiac disease. Exclusion criteria included age <18 years, pregnancy, or history of recent chest trauma. The Queen's Medical Center Institutional Review Board approved this study.
The time of pulmonary artery catheter insertion was defined as the time of study entry ([T.sub.0]). A continuous cardiac output pulmonary artery catheter (Edwards LifeSciences Corporation, Irvine, California, U.S.A.) was inserted after informed consent was obtained from the patient or designated surrogate and this catheter was used for titration of fluids and vasoactive agents. All clinical decision-making, including the decision to place a pulmonary artery catheter, was made by the surgical intensivist team assigned to the SICU while the patient was hospitalised. All surgical and trauma patients admitted to the SICU are admitted specifically to this team for management. A detailed cardiac history was obtained from the patient and/or family members as well as from the medical record. Predefined parameters for therapy in this setting were based on a previous trial published by our group (21). This protocol was followed independent of the patient's cardiac history or troponin I levels.
In brief, patients were treated to a mean arterial pressure of [less than or equal to] 65 mmHg, systolic pressure [greater than or eqaul to] 100 mmHg or within 40 mmHg from a known baseline, heart rate <100 /min and a urine output [greater than or eqaul to] 1 nil/kg/h. Additionally, treatment goals also included achieving a lactate level that demonstrated a decreasing trend, if initially elevated. The goal was also to maintain the mixed venous oxygen saturation (Sv[O.sub.2]) [greater than or equal to] 70% and oxygen delivery (D[O.sub.2)[greater than or eqaul to] 600 ml/min/[m.sup.2]. This was accomplished by infusing crystalloid or colloid of 250 to 500 ml, or blood infusion if the haemoglobin was [less than or equal to] 100 g/1, in order to achieve a pulmonary artery occlusion pressure (PAOP) of 15 to 18 mmHg. The PAOP was measured at end expiration, or measured with positive end expiratory pressure (PEEP) stopped for < 1 second if the PEEP was > 10 cm [H.sub.2]O. Once this PAOP was achieved, fluid resuscitation was deemed adequate and a dobutamine infusion at a rate of 2 to 5 [micro]g/kg/min was started if the systolic blood pressure was >100 mmHg. Dobutamine infusion was titrated to achieve predetermined treatment goals up to 20 [micro]g/min/[m.sup.2], or until patients became tachycardic (heart rate >100 /min). All patients who received noradrenaline or adrenaline were given infusions starting at 1 pg/min titrated to a predetermined blood pressure of [greater than or equal to] 100 mmHg, if patients were hypotensive despite an adequate PAOP of 15 to 18 mmHg.
Serum troponin I levels were drawn at [T.sub.0] and every six to eight hours subsequently, if there was ongoing tachycardia, hypotension or arrhythmias requiring treatment, for a duration of 24 to 48 hours after the initial sample was obtained. This was done to evaluate patients for ongoing myocardial dysfunction and to confirm that the levels of troponin I had peaked. Troponin I levels were measured using the Access Analyzer (Beckman Coulter Inc., Fullerton, California, U.S.A.) and a level of >0.1 [micro]g/1 was considered elevated per manufacturer guidelines. Age, gender and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were recorded. Patient data were recorded hourly and included heart rate, blood pressure, central venous pressure, PAOP, cardiac index (CI), D[O.sub.2] Sv[O.sub.2] and vasopressor or inotrope use. Hospital mortality, ventilator days, SICU length of stay (LOS) and overall hospital LOS measured in days, were assessed and recorded by blinded investigators.
Results are presented as mean [+ or -] standard deviation (SD) for continuous variables and as percentages for categorical variables. Two-tailed t-tests were used for comparison of continuous variables and Chi square tests were used for comparison of categorical variables. A P value of <0.05 was considered statistically significant.
Sixty-six consecutive patients with severe sepsis or septic shock were studied. Demographics are presented in Table 1.
Troponin I was elevated in 42 patients (64%) at To with a mean value of 1.65 [+ or -] 3.99 [micro]g/1. Subsequent results of troponin I levels obtained in patients with an elevation at [T.sub.0] remained elevated for the duration of measurement. There was no instance when a patient who had a normal reference range troponin I level at [T.sub.0] was found to develop an elevated level on retesting due to persistent tachycardia, hypotension or arrhythmias requiring treatment. Therefore, analysis of results was done using the troponin I value at [T.sub.0]. Comparison of patients with and without troponin I elevation are presented in Table 2.
For the 17 patients with a pre-existing cardiac history with elevations of troponin I, admitting diagnoses included necrotising fasciitis (two patients), acute cholecystitis (two patients), perforated sigmoid diverticulitis (two patients) and one each with the following diagnoses: pancreatic cancer, colon cancer, gangrenous small bowel obstruction due to adhesions, non-gangrenous small bowel obstruction due to adhesions, right foot gangrene, peripheral vascular disease, enterocutaneous fistula, small bowel volvulus, perforated duodenal ulcer, pelvic fracture and right hip fracture. Ten patients were admitted to the SICU immediately postoperatively on the day of surgery, three were admitted on postoperative day one, one each was admitted on postoperative days three, four and eight; and one was admitted directly from the emergency room on hospital day one and did not undergo surgery.
For the six patients with a pre-existing history of cardiac disease without troponin I elevation, admitting diagnoses included: perforated sigmoid diverticulitis, pelvic abscess, ruptured abdominal aortic aneurysm, development of acute renal failure and respiratory failure four days after admission to the general inpatient ward for observation after a low impact fall, perforated jejunum and perforated acute cholecystitis. Four patients were admitted to the SICU immediately postoperatively on the day of surgery, one on postoperative day eight and one on hospital day four.
There were no significant differences in gender or APACHE II scores. Patients with elevated troponin I appeared to be older (67.2 [+ or -] 18 vs. 59.9 [+ or -] 16 years, P=0.10) and more likely to have cardiac disease (40% vs. 25%, P=0.32), although this did not reach statistical significance. Oxygen delivery at [T.sub.o] was significantly reduced in the elevated troponin I group compared to the normal level troponin I group (528 [+ or -] 152 vs. 624 [+ or -] 157 ml/min/m2, P=0.02). Thirty-six percent of these patients required inotropic support to maintain oxygen delivery at the predetermined goal. This observation did not translate into demonstrable differences in ventilator days, SICU or hospital LOS between these two groups.
Four patients in the group of 17 patients with preexisting cardiac history and troponin I elevations had undergone prior coronary reperfusion (three coronary artery bypass grafting, one percutaneous transluminal coronary angioplasty). Three patients in the group of six patients with pre-existing cardiac history and no elevation of troponin I had undergone prior coronary reperfusion (two coronary artery bypass grafting, one percutaneous transluminal coronary angioplasty). The difference between these two groups was not significant (P=0.97). When subgroup analysis was done on the patients with a prior cardiac history, comparing the number of patients who underwent coronary reperfusion procedures in the group of 17 patients with troponin I elevation and the group of six patients with no elevation of troponin I, there was again no significant difference between the two groups (P=0.49).
Twenty-three patients had a history of cardiac disease as defined above. There were 43 patients without a history of cardiac disease. In this group, admitting diagnoses included necrotising fasciitis (six patients), traumatic brain injury (five patients), acute cholecystitis (three patients), bladder cancer (three patients), gangrenous small bowel obstruction due to adhesions (two patients), perforated peptic ulcer disease (two patients), hip fracture (two patients), pancreatic cancer (two patients); and one each with sigmoid cancer, urosepsis, perforated oesophagus, non-gangrenous small bowel obstruction due to adhesions, thoracic spine fracture of the ninth vertebral body with paraplegia, caecal gangrene, right hydronephrosis with urosepsis, subdural haemorrhage, splenic laceration, oesophageal cancer, duodenal cancer, colon cancer with postoperative small bowel obstruction, gastric cancer, degenerative disc disease with spinal stenosis, cervical spine fracture of second vertebral body, mangled extremities due to crush injury on a ship five days earlier, radiation ileitis with perforated ileum and necrotising pancreatitis. Nineteen patients were admitted to the SICU immediately postoperatively, two were admitted on postoperative day one, two on postoperative day three and one each on postoperative days five, six, seven, nine, 20 and 26. Of those patients who did not undergo surgery, 10 were admitted to the SICU on the day of hospital admission, two on hospital day one and one on hospital days two and five.
Comparison of those with and without pre-existing cardiac disease is presented in Table 3. Gender, APACHE II scores and sources of infection did not differ between groups. Patients with pre-existing cardiac disease were significantly older (P <0.001) and had lower CI (P=0.006) and not unexpectedly therefore, a lower D[O.sub.2] (P=0.002) at [T.sub.0] Similar vasopressor and inotropic requirements were observed regardless of whether there was a history of cardiac disease. Mortality was significantly higher in the group with a cardiac history (44% vs. 16%, P=0.03). There were no differences in ventilator days, SICU or hospital LOS.
Mortality was evaluated in the presence and absence of both troponin I elevation and preexisting cardiac disease. Patients with both troponin I elevation at [T.sub.0] and a prior history of cardiac disease had an in-hospital mortality of 47%, the highest of any subgroup. Mortality was due primarily to multisystem organ failure. Patients with elevations of only troponin I, and no history of pre-existing cardiac disease, did not demonstrate a higher mortality compared to patients with no elevation of troponin I and no prior history of cardiac disease.
Our study specifically investigates the impact of pre-existing cardiac history and troponin I elevations in surgical patients with severe sepsis or septic shock treated with a pulmonary artery catheter. We report a 64% incidence of troponin I elevation, which is consistent with previous publications (12-19). Previous authors have noted a high incidence of troponin I elevation in septic patients at different points in time during their hospital course. Ver Elst et al reported troponin I elevation in 39% of patients with septic shock at the time of their study entry. All outcome data were based upon the 50% of patients (n=23 patients) who had troponin I elevation within the first 48 hours of study (13). Ammann et al followed 58 patients with the systemic inflammatory response syndrome, sepsis or septic shock in two medical intensive care units and reported troponin I and T elevation in 63% of patients within the first eight days of observation (15). Other reports have noted troponin I elevation in 43 to 85% of patients with sepsis (12,14,18,19). Elevations of troponin T have likewise been reported by Spies et al who found 69% of 26 septic patients had levels indicative of myocardial injury (16). Our findings demonstrate troponin I is frequently elevated at the onset of severe sepsis or septic shock when subsequent haemodynamic interventions may be most effective (22).
Several studies have shown an association between troponin I elevation and increased mortality. The prognostic value of troponin I elevation in acute coronary syndrome, in terms of morbidity and mortality, is well documented (9,23,24). Recently, the importance of troponin I as a surrogate marker for risk stratification and prognosis in patients with other critical illnesses has been appreciated. Relos et al examined 2591 SICU patients for troponin I elevation at a tertiary care hospital (11). Even moderate elevations of troponin I (0.4 to 2.0 [micro]g/l) in postsurgical patients were associated with higher mortality, longer intensive care unit stay and longer hospital stay.
We found an in-hospital mortality of 29% for patients with severe sepsis or septic shock and troponin I elevation at [T.sub.0], compared to 21% for patients without troponin I elevation. This difference did not reach statistical significance, contrasting previous reports. Three studies have demonstrated a statistically significant increase in mortality in patients with troponin elevation in the setting of sepsis or other critical illness. Ammann et al examined 58 critically ill medical intensive care unit patients, most of whom had the systemic inflammatory response syndrome, sepsis or septic shock (15). In 32 of these patients with troponin I or T elevation, 30-day mortality was 22.4%, compared to 5.2% in 26 patients without troponin I or T elevation (P <0.018). Spies et al found elevations of troponin T in 18 of 26 septic patients in a SICU, with a mortality of 83% (16). This was significantly higher than the 37% mortality for those septic patients without troponin T elevation. This group comprised only three out of eight patients without troponin T elevation and this may have resulted in a type I error. Furthermore, the overall mortality of 69% in this series is considerably higher than what is typically reported in the literature, in part probably due to the relatively higher mean APACHE II score of 48, reported for this patient cohort. Mehta et al examined 37 critically ill patients with septic shock and obtained troponin I levels at study entry, 24 hours and 48 hours. Troponin I elevation was present at some time point in 43% of patients and proved to be an independent predictor of death and prolonged intensive care unit stay". However, Mehta et al excluded from analysis patients with pre-existing cardiac disease, a significant group of patients typically admitted to the intensive care unit and a group that comprised 35% of patients in our study.
Additional studies have demonstrated trends toward increased mortality in septic patients with troponin I elevation, but they have been underpowered due to the small number of patients in these studies (12-14-16-19).
There was no statistically significant difference in mortality between patients with and without troponin I elevations in our study population. This is in contradistinction to previous studies, but there are several differences between our study and previous studies. First, we used a pulmonary artery catheter and resuscitated patients to pre-defined treatment goals. Second, the time of measurement of troponin I was at study entry. Patients with elevated troponin I had reduced D[O.sub.2] at [T.sub.0] compared to patients without troponin I elevation. These patients were immediately and aggressively treated to goal D[O.sub.2] values using a combination of volume infusion, red cell transfusion and inotropic and/or vasopressor support utilising an established treatment algorithms (21). The differences in D[O.sub.2] between patient groups were thus reduced or eliminated early in their SICU course, potentially reducing morbidity and mortality in patients with elevated troponin I. The mortality reported in our study is consistent with the lower end of reported values for this group of patients.
The mean value of troponin I elevation in our study was relatively low (1.65 [+ or -] 3.99 [micro] g/1) in comparison to values seen in acute coronary syndrome. These levels may reflect mitochondrial dysfunction with reversible cardiac injury and transitory release of troponin I, as opposed to myofibrillar degradation common in myocardial infarccton (25). Elevated troponin I and T have been found in numerous other noncardiac settings including endurance exercise26-28, subarachnoid haemorrhage (29,30), renal failure (31,32) and pulmonary embolism (33,34) However, in each of these settings, elevated troponin I or T has been accompanied by either echocardiographic evidence of myocardial dysfunction or an increased risk of death. Troponin elevation in sepsis may similarly be of prognostic value.
Our study may have been underpowered to detect a statistically significant difference in mortality between patients with and without troponin I elevations. The small number of patients in each subgroup may have resulted in a type II error and may have limited our ability to demonstrate significant differences between each. Furthermore, although all patients in this study met predefined criteria for sepsis or septic shock, the primary admitting diagnoses comprised a heterogeneous group, which also may have potentially impacted our results. However, the study group typifies the mix of patients often encountered in an SICU.
We did find, however, a strong association between pre-existing cardiac disease and mortality in septic patients. Patients with a prior history of cardiac disease had an in-hospital mortality of 44% and were almost three times as likely to die from severe sepsis or septic shock compared to those without a prior history of cardiac disease. Previous studies have either not specifically examined the portion of patients enrolled with pre-existing cardiac disease (11,14,15,17), or the sample size was too small to find a statistically significant difference (12,13,16), or patients with pre-existing cardiac disease were excluded altogether (18). Raper et al examined normotensive, septic patients with and without coronary artery disease and found no difference in mortality, although CI was significantly reduced in patients with coronary artery disease (35). Ver Elst et al examined 46 patients with septic shock, of whom 10 had a prior history of myocardial infarction (13). Within this subgroup, nine of 10 patients had an elevated troponin I and six patients ultimately died. A prospective survey of 11,828 intensive care unit admissions in France, including 742 patients with severe sepsis, identified chronic cardiovascular insufficiency as an independent risk factor for increased mortality (36). The study was based on registry data and the nature of the cardiovascular insufficiency was not further defined other than by APACHE II and the Simplified Acute Physiology Score criteria.
The fact that we were able to demonstrate increased mortality in severely septic patients or septic shock patients with underlying cardiac disease could be due to the specific characteristics of our study population. Hypotension or organ dysfunction was present in all of our patients at study entry by definition. This emphasises the importance of baseline, premorbid, cardiac function compared to patients with systemic inflammatory response syndrome or sepsis alone. In our patient population, cardiac disease was prevalent (35% of patients) and the patients were older relative to other publications (19). The argument may be made that overaggressive attempts using our predefined treatment algorithm to increase CI, and thus D[O.sub.2], in this subgroup of older patients may actually be deleterious and resulted in the increased mortality observed in the group of patients with pre-existing cardiac disease. Contrary to this, we published the results of a randomised trial that demonstrated a statistically significant improvement in survival rate in patients between 50 to 75 years of age with a diagnosis of systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock and/or acute respiratory distress syndrome with treatment goal to achieve a D[O.sub.2] of [graeter than o equal to] 600 ml/minute/[m.sup.2]. Although there was no benefit, there was also no difference in mortality rate in the age group > 75 years of age in this trial (21).
Cardiac reperfusion status did not appear to affect the results of this study. The number of patients who underwent coronary artery reperfusion procedures in both groups of patients with a prior cardiac history (with troponin I elevation and without troponin I elevation) were small. The difference between both groups was not statistically significant, even with subgroup analysis. Moreover, renal failure, commonly encountered in septic patients, may affect the clearance of both troponins I and T Based on serum creatinine levels as a biomarker, there was no difference in the prevalence of renal insufficiency or failure between the groups examined (19,31-32).
In summary, myocardial injury commonly occurs in patients with severe sepsis and septic shock. These patients, who present with troponin I elevation and/or pre-existing cardiac disease, are likely to have myocardial dysfunction demonstrated by invasive monitoring. Pre-existing cardiac disease has been associated with increased mortality in patients with severe sepsis and septic shock. In our study, troponin I elevation in the absence of pre-existing cardiac disease did not predict a significant increase in mortality. This may be explained by differences in our patient selection, timing of troponin measurements and the early use of a pulmonary artery catheter to reach perfusion and treatment goals, although the utility of pulmonary artery catheters to affect patient outcome has been called into question based on randomised trial data (37).
A history of pre-existing cardiac disease, and not troponin I elevation, was found to be a valuable marker of significant cardiac compromise in severe sepsis and septic shock patients in this study. If this finding is verified by others, in larger studies, it may alert clinicians to the increased risk of mortality in this cohort of patients with preexisting cardiac disease. This may further enable early application of goal-directed therapies. Early implementation of goal-directed therapies may improve outcome in patients with sepsis and septic shock, although this concept is not universally accepted. In this study all patients were treated according to a predefined institutional protocol and thus this study was not designed to investigate the impact of early implementation of goal-directed therapy on outcome in this group of patients. A randomised controlled trial is necessary to address this.
Given that this was an observational study, we propose to study a much larger group of patients to include both nonseptic patients and septic patients admitted to the SICU, not requiring a pulmonary artery catheter, to determine if elevated troponin I levels and pre-existing cardiac disease are true surrogate markers and reliable discriminatory parameters of risk stratification and prognostication in septic surgical patients.
Accepted for publication on August 22, 2007.
(1.) Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29:1303-1310.
(2.) Krishnagopalan S, Kumar A, Parrillo JE, Kumar A. Myocardial dysfunction in the patient with sepsis. Corr Opin Crit Care 2002; 8:376-388.
(3.) Cain BS, Meldrum DR, Dinarello CA, Meng X, Joo KS, Banerjee A, Harken AH. Tumor necrosis factor-alpha and interleukin-1 beta synergistically depree human myocardial function. Crit Care Med 1999; 27:1309-1318.
(4.) Kumar A, Thota V, Dee L, Olson J, Uretz E, Parrillo JE. Tumor necrosis factor-alpha and interleukin-1 beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J Exp Med 1996; 183:949-958.
(5.) Cunnion RE, Schaer GL, Parker MM, Natanson C, Parrillo JE. The coronary circulation in human septic shock. Circulation 1986; 73:637-644.
(6.) Dhainaut JF, Huyghebaert MF, Monsallier JF, Lefevre G, Dall'Ava-Santucci J, Brunet F et al. Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock. Circulation 1987; 75:533-541.
(7.) Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: Executive summary and recommendations. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on the management of patients with unstable angina). Circulation 2000; 102:1193-1209.
(8.) Myocardial infarction redefined-a consensus document of the Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction. J Am Coll Cardiol2000; 36:959-969.
(9.) Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996; 335:1342-1349.
(10.) Heidenreich PA, Alloggiamento T, Melsop K, McDonald KM, Go AS, Hlatky MA. The prognostic value of troponin in patients with non-ST-elevation acute coronary syndromes: A meta-analysis. J Am Coll Cardiol2001; 38:478-485.
(11.) Relos RP, Hasinoff IK, Beilman GJ. Moderately elevated serum troponin concentrations are associated with increased morbidity and mortality rates in surgical intensive care unit patients. Crit Care Med 2003; 31:2598-2603.
(12.) Arlati S, Brenna S, Prencipe L, Marocchi A, Casella GP, Lanzani M et al. Myocardial necrosis in ICU patients with acute non-cardiac disease: a prospective study. Intensive Care Med 2000; 26:31-37.
(13.) ver Elst KM, Spapen HD, Nguyen DN, Garbar C, Huyghens LP, Gorus FK. Cardiac troponins I and T are biological markers of left ventricular dysfunction in septic shock. Clin Chem 2000; 46:650-657.
(14.) Ammann P, Fehr T, Minder EI, Gunter C, Bertel O. Elevation of troponin I in sepsis and septic shock. Intensive Care Med 2001; 27:965-969.
(15.) Ammann P, Maggiorini M, Bertel O, Haenseler E, JollerJemelka HI, Oechslin E et al. Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. J Am Coll Cardiol2003; 41:2004-2009.
(16.) Spies C, Haude V, Fitzner R, Schroder K, Overbeck M, Runkel N et al. Serum cardiac troponin T as a prognostic marker in early sepsis. Chest 1998; 113:1055-1063.
(17.) Turner A, Tsamitros M, Bellomo R. Myocardial cell injury in septic shock. Crit Care Med 1999; 27:1775-1780.
(18.) Mehta NJ, Khan IA, Gupta V, Jani K, Gowda RM, Smith PR. Cardiac troponin I predicts myocardial dysfunction and adverse outcome in septic shock. Int J Cardiol2004; 95:13-17.
(19.) Maeder M, Fehr T, Rickli H, Ammann P Sepsis-associated myocardial dysfunction. Diagnostic and prognostic impact of cardiac troponins and natriuretic peptides. Chest 2006; 129:1349-1366.
(20.) Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/ SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101:1644-1655.
(21.) Yu M, Burchell S, Hasaniya NW, Takanishi DM, Myers SA, Takiguchi SA. Relationship of mortality to increasing oxygen delivery in patients > 50 years of age: a prospective randomized study. Crit Care Med 1998; 26:1011-1019.
(22.) Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B et al. Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-1377.
(23.) Horwich TB, Patel J, MacLellan WR, Fonarow GC. Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 2003; 108:833-838.
(24.) Apple FS, Murakami MM, Quist HH, Pearce LA, Wieczorek S, Wu AH. Prognostic value of the ortho vitros cardiac troponin I assay in patients with symptoms of myocardial ischemia. Am J Clin Pathol2003; 120:114-120.
(25.) Crouser ED, Julian MW, Blaho DV, Pfeiffer DR. Endotoxininduced mitochondrial damage correlates with impaired respiratory activity. Crit Care Med 2002; 30:276-284.
(26.) Neumayr G, Pfister R, Mitterbauer G, Maurer A, Gaenzer H, Sturm W et al. Effect of the "Race Across The Alps" in elite cyclists on plasma cardiac troponins I and T Am J Cardiol 2002; 89:484-486.
(27.) Rifai N, Douglas PS, O'Toole M, Rimm E, Ginsburg GS. Cardiac troponin T and I, echocardiographic [correction of electrocardiographic] wall motion analyses, and ejection fractions in athletes participating in the hawaii ironman triathlon. Am J Cardiol1999; 83:1085-1089.
(28.) Neumayr G, Gaenzer H, Pfister R, Sturm W, Schwarzacher SP, Eibl G et al. Plasma levels of cardiac troponin I after prolonged strenuous endurance exercise. Am J Cardiol2001; 87:369-371.
(29.) Deibert E, Barzilai B, Braverman AC, Edwards DF, Aiyagari V, Dacey R et al. Clinical significance of elevated troponin I levels in patients with nontraumatic subarachnoid hemorrhage. J Neurosurg 2003; 98:741-746.
(30.) Parekh N, Venkatesh B, Cross D, Leditschke A, Atherton J, Miles W et al. Cardiac troponin I predicts myocardial dysfunction in aneurysmal subarachnoid hemorrhage. J Am Coll Cardiol2000; 36:1328-1335.
(31.) Wayand D, Baum H, Sch5tzle G, Schdrf J, Neumeier D. Cardiac troponin T and I in end-stage renal failure. Clin Chem 2000; 46:1345-1350.
(32.) Freda BJ, Tang WH, Van Lente F, Peacock WF, Francis GS. Cardiac troponins in renal insufficiency: review and clinical implications. J Am Coll Cardiol2002; 40:2065-2071.
(33.) Giannitsis E, Muller-Bardorff M, Kurowski V, Weidtmann B, Wiegand U, Kampmann M et al. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism. Circulation 2000; 102:211-217.
(34.) Konstantinides S, Geibel A, Olschewski M, Kasper W, Hruska N, Jackle S et al. Importance of cardiac troponins I and T in risk stratification of patients with acute pulmonary embolism. Circulation 2002; 106:1263-1268.
(35.) Raper RF, Sibbald WJ. The effects of coronary artery disease on cardiac function in nonhypotensive sepsis. Chest 1988; 94:507-511.
(36.) Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A et al. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults: a multicenter prospective study in intensive care units. JAMA 1995; 274:968-974.
(37.) Richard C, Warszawski J, Anguel N, Deye N, Combes A, Barnoud D et al. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a randomized controlled trial. JAMA 2003; 290:2713-2720.
E.C. SCOTT *, H.C. HO [dagger], M. YU [double dagger], A.D. CHAPITAL [section], W, KOSS [section], D.M. TAKANISHI JR **
Divisions of Trauma and Surgical Critical Care, Department of Surgery, University of Hawaii, John A. Burns School of Medicine and The Queen's Medical Center, Honolulu, Hawaii, United States of America
* M.D., Surgical Critical Care Fellow, Division of Surgical Critical Care.
[dagger] M.D., Assistant Professor of Surgery and Division Chief of 13.
[double dagger] M.D., Professor, Associate Chair of Surgery and Division Chief of Surgical Critical Care.
[section] M.D., Assistant Professor of Surgery.
** M.D., Associate Professor and Chairman. Accepted for publication on August 22,2007.
Address for reprints: Dr D. M. Takanish Jr., University of Hawaii, John A. Burns School of Medicine, Department of Surgery, 1356 Lusitana Street, 6th Floor, Honolulu, Hawaii 96813, U.S.A.
TABLE 1 Characteristics of the study population Patients n = 66 Age (years) 64.6 [+ or -] 17 Male 39 (59%) APACHE II 21 [+ or -] 5.6 Severe sepsis 24 (36%) Septic shock 42 (64%) Source of sepsis Abdomen 35 (53%) Pulmonary 20 (30%) Necrotising fasciitis 8 (12%) Urinary tract 3 (5%) Type of surgery Abdominal 24 (36%) Pulmonary 1 (2%) Debridement (necrotising fasciitis) 6 (9%) Urinary tract 2 (3%) Orthopaedic 3 (5%) Peripheral vascular disease 2 (3%) Prior cardiac history 23 (35%) APACHE II = Acute Physiology and Chronic Health Evaluation II score. TABLE 2 Patient characteristics and haemodynamic parameters by presence or absence of troponin I elevation Troponin No troponin P I elevation I elevation value (n=42) (n=24) Male : female 26 : 16 13 : 11 0.72 Age (years) 67.2 [+ or -] 18 59.9 [+ or -] 16 0.10 APACHE II 21.6 [+ or -] 5 20.1 [+ or -] 5 0.32 Cardiac history 17 (40%) 6 (25%) 0.32 Prior coronary 4 (10%) 3 (13%) 0.97 reperfusion procedure Patients requiring 25 (60%) 14 (58%) 0.87 vasopressors Patients requiring 15 (36%) 5 (21%) 0.32 inotropes Renal insufficiency 16 (38%) 8 (33%) 0.90 CI * (1/min/[m.sup.2]) 3.72 [+ or -] 1.3 4.16 [+ or -] 1.3 0.20 D[O.sub.2] * 528 [+ or -] 152 624 [+ or -] 157 0.02 (ml/min/[m.sup.2]) SV[O.sub.2] * (%) 73 [+ or -] 6.9 74 [+ or -] 7.8 0.52 SICU days 17.2 [+ or -] 13 17.9 [+ or -] 16 0.85 Ventilator days 13.2 [+ or -] 14 15.2 [+ or -] 15 0.58 Hospital days 33.0 [+ or -] 28 37.3 [+ or -] 28 0.55 Mortality 12 (29%) 5 (21%) 0.69 * Value at [T.sub.0]. APACHE II=Acute Physiology and Chronic Health Evaluation II Score, CI=cardiac index, D[O.sub.2]=oxygen delivery, SV[O.sub.2]=mixed venous oxygen saturation, SICU days=surgical intensive care unit length of stay. TABLE 3 Patient characteristics and haemodynamic parameters by presence or absence of pre-existing cardiac disease Pre-existing No cardiac P value cardiac disease disease (n=23) (n=43) Male : female 14 : 9 25 : 18 0.96 Age (years) 75 [+ or -] 9 59 [+ or -] 18 0.0002 APACHE II 22 [+ or -] 4 21 [+ or -] 6 0.48 Elevated troponin I * 17 (74%) 25 (58%) 0.32 Patients requiring 14 (61%) 25 (58%) 0.96 vasopressors Patients requiring 9 (39%) 11 (26%) 0.39 inotropes Renal insufficiency 11 (48%) 13 (30%) 0.25 CI * (1/min/[m.sup.2]) 3.3 [+ or -] 1.0 4.2 [+ or -] 1.3 0.006 D[O.sub.2] * 483 [+ or -] 134 607 [+ or -] 157 0.002 (ml/min/[m.sup.2]) SV[O.sub.2] * (%) 71 [+ or -] 8 74 [+ or -] 6 0.09 SICU days 17.2 [+ or -] 15 18.5 [+ or -] 16 0.74 Ventilator days 14.4 [+ or -] 16 14.7 [+ or -] 15 0.94 Hospital days 35.6 [+ or -] 33 34.9 [+ or -] 26 0.92 Mortality 10 (44%) 7 (16%) 0.03 * Value at [T.sub.0]. APACHE II=Acute Physiology and Chronic Health Evaluation II Score, CI=cardiac index, D[O.sub.2]=oxygen delivery, SV[O.sub.2]=mixed venous oxygen saturation, SICU days=surgical intensive care unit length of stay. FIGURE 1: In-hospital mortality in 66 patients with severe sepsis or septic shock. (Group 1 vs. 4, P=0.12; group 2 vs. 4, P=0.07; group 3 vs. 4, P=0.92; group 1 vs. 3, P=0.77). (-) Cardiac history=no pre-existing cardiac disease, (+) Cardiac disease=pre-existing cardiac disease, (-) Troponin I=no elevation of troponin I, (+) Tropinin I=elevation of tropinin I, n=number of patients in each group. Group 1 (n=18) 17% (-) Cardiac history (-) Troponin I Group 2 (n=25) 16% (-) Cardiac history (+) Troponin I Group 3 (n=6) 33% (+) Cardiac history (-) Troponin I Group 4 (n=17) 47% (+) Cardiac history (+) TRoponin I Note: Table made from bar graph.
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|Author:||Scott, E.C.; Ho, H.C.; Yu, M.; Chapital, A.D.; Koss, W.; Takashi, D.M., Jr.|
|Publication:||Anaesthesia and Intensive Care|
|Article Type:||Clinical report|
|Date:||Jan 1, 2008|
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