Epidemiology of secondary fluid bolus therapy for infection-associated hypotension.

OBJECTIVE: Fluid bolus therapy (FBT) is a common therapy for hypotensive sepsis, but no studies have compared primary FBT (in the first 6 hours after presentation to the emergency department [ED]) with secondary FBT (6-24 hours after presentation to the ED). We aimed to describe the patterns of use, physiological sequelae and outcomes of patients with hypotensive sepsis who were treated with primary FBT or combined primary and secondary FBT (secondary FBT). DESIGN, SETTING AND PATIENTS: A retrospective observational study of patients with hypotensive sepsis presenting to the ED of a tertiary hospital from 1 January to 31 December 2010. RESULTS: We studied 100 consecutive eligible patients (primary FBT, n = 52; secondary FBT, n = 48). Secondary FBT occurred in the ward (n = 31) or in the intensive care unit (n = 17). More patients receiving secondary FBT had sepsis with undefined focus or septic shock (P = 0.005, P = 0.0001, respectively), and fewer patients receiving secondary FBT had pneumonia (P = 0.0004). At 24 hours, the use of secondary FBT was similar for patients admitted to the ward and the ICU, and represented about 40% of all secondary fluids given. The volume of any bolus was greater during primary resuscitation, and the size of physiological changes associated with FBT diminished with time. The mortality rate at 28 days was 27%, and was similar for ward and ICU admissions. CONCLUSIONS: Secondary FBT is given to about half of patients presenting with hypotensive sepsis, takes place in wards more often than in the ICU and delivers a significant proportion of overall fluids, but is associated with limited changes in measured physiological variables.

Primary fluid bolus therapy for infection-associated hypotension in the emergency department.

OBJECTIVES: The physiological changes associated with fluid bolus therapy (FBT) for patients with infection-associated hypotension in the emergency department (ED) are poorly understood. We describe the physiological outcomes of FBT in the first 6 hours (primary FBT) for patients presenting to the ED with infection-associated hypotension. METHODS: We studied 101 consecutive ED patients with infection and a systolic blood pressure (SBP)<100 mmHg who underwent FBT in the first 6 hours. RESULTS: We screened 1123 patients with infection and identified 101 eligible patients. The median primary FBT volume given was 1570 mL (interquartile range, 1000- 2490 mL). The average mean arterial pressure (MAP) did not change from admission to 6 hours in the whole cohort, or in patients who were hypotensive on arrival at the ED. However, the average MAP increased from its lowest value during the first 6 hours (66 mmHg [SD, 10 mmHg]) to its value at 6 hours (73 mmHg [SD, 12 mmHg]; P<0.001). The mean heart rate, body temperature, respiratory rate and plasma creatinine level decreased (P<0.05). In patients who were severely hypotensive (SBP<90 mmHg) on arrival at the ED, the MAP increased from 54 mmHg (SD, 8 mmHg) to 70 mmHg (SD, 14 mmHg) (P<0.001). At 6 hours, however, SBP was still <100 mmHg in 44 patients and <90 mmHg in 17 patients. When noradrenaline was used, in 10 patients, hypotension was corrected in all 10 and the MAP increased from 58 mmHg (SD, 9 mmHg) to 75 mmHg (SD, 13 mmHg). CONCLUSION: Among ED patients admitted to an Australian teaching hospital with infection, hypotension was uncommon. FBT for hypotension was limited in volumes given and failed to achieve a sustained SBP of >100 mmHg in 40% of cases. In contrast, noradrenaline therapy corrected hypotension in all patients who received it.

Use of ivabradine and atorvastatin in emergent orthopedic lower limb surgery and computed tomography coronary plaque imaging and novel biomarkers of cardiovascular stress and lipid metabolism for the study and prevention of perioperative myocardial infarction: study protocol for a randomized controlled trial.

BACKGROUND: The incidence of perioperative myocardial infarction (PMI) globally is known to be around 2 to 3% and can prolong hospitalization, increased morbidity and mortality. Little is known about the pathophysiology and risk factors for PMI. We investigate the presence of elevated novel cardiac markers and preoperative coronary artery plaque through contemporary laboratory techniques to determine the correlation with PMI, as well as studying ivabradine and atorvastatin as protective pharmacotherapies against PMI in the context of orthopedic surgery. METHODS/DESIGN: We aim to enroll 200 patients aged above 60 years who suffer from neck of femur fracture requiring surgery. Patients will be randomized to four arms (no study drugs, atorvastatin only, ivabradine only and ivabradine and atorvastatin). Our primary outcome is incidence of PMI. All patients will receive an electrocardiogram, cardiac echocardiography, measurement of novel cardiac biomarkers and computed tomography (CT) coronary angiography. A telephone interview post discharge will be conducted at 30 days, 60 days and 1 year. DISCUSSION: We postulate that ivabradine and atorvastatin will reduce the rate and magnitude of PMI following surgery by reducing heart rate and attenuating catecholamine-induced tachycardia postoperatively. Secondly, we postulate that postoperative reduction in heart rate and catecholamine-induced tachycardia with ivabradine will correlate with a reduction in cardiovascular novel biomarkers which will reduce atrial stretch and postoperative incidence of arrhythmia. We aim to demonstrate that treatment with ivabradine and atorvastatin will cause a reduction in the incidence and magnitude of PMI, the benefit of which is derived primarily in patients with greater atherosclerotic burden as measured by higher CT coronary calcium scores. TRIAL REGISTRATION: This study protocol has been listed in the Australia New Zealand Clinical Trial Registry (registration number: ACTRN12612000340831) on 23 March 2012.