Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial.

BACKGROUND: Immobilisation predicts adverse outcomes in patients in the surgical intensive care unit (SICU). Attempts to mobilise critically ill patients early after surgery are frequently restricted, but we tested whether early mobilisation leads to improved mobility, decreased SICU length of stay, and increased functional independence of patients at hospital discharge. METHODS: We did a multicentre, international, parallel-group, assessor-blinded, randomised controlled trial in SICUs of five university hospitals in Austria (n=1), Germany (n=1), and the USA (n=3). Eligible patients (aged 18 years or older, who had been mechanically ventilated for <48 h, and were expected to require mechanical ventilation for ≥24 h) were randomly assigned (1:1) by use of a stratified block randomisation via restricted web platform to standard of care (control) or early, goal-directed mobilisation using an inter-professional approach of closed-loop communication and the SICU optimal mobilisation score (SOMS) algorithm (intervention), which describes patients' mobilisation capacity on a numerical rating scale ranging from 0 (no mobilisation) to 4 (ambulation). We had three main outcomes hierarchically tested in a prespecified order: the mean SOMS level patients achieved during their SICU stay (primary outcome), and patient's length of stay on SICU and the mini-modified functional independence measure score (mmFIM) at hospital discharge (both secondary outcomes). This trial is registered with ClinicalTrials.gov (NCT01363102). FINDINGS: Between July 1, 2011, and Nov 4, 2015, we randomly assigned 200 patients to receive standard treatment (control; n=96) or intervention (n=104). Intention-to-treat analysis showed that the intervention improved the mobilisation level (mean achieved SOMS 2·2 [SD 1·0] in intervention group vs 1·5 [0·8] in control group, p<0·0001), decreased SICU length of stay (mean 7 days [SD 5-12] in intervention group vs 10 days [6-15] in control group, p=0·0054), and improved functional mobility at hospital discharge (mmFIM score 8 [4-8] in intervention group vs 5 [2-8] in control group, p=0·0002). More adverse events were reported in the intervention group (25 cases [2·8%]) than in the control group (ten cases [0·8%]); no serious adverse events were observed. Before hospital discharge 25 patients died (17 [16%] in the intervention group, eight [8%] in the control group). 3 months after hospital discharge 36 patients died (21 [22%] in the intervention group, 15 [17%] in the control group). INTERPRETATION: Early, goal-directed mobilisation improved patient mobilisation throughout SICU admission, shortened patient length of stay in the SICU, and improved patients' functional mobility at hospital discharge. FUNDING: Jeffrey and Judy Buzen.

The arterial blood pressure associated with terminal cardiovascular collapse in critically ill patients: a retrospective cohort study.

INTRODUCTION: Liberal and overaggressive use of vasopressors during the initial period of shock resuscitation may compromise organ perfusion and worsen outcome. When transiently applying the concept of permissive hypotension, it would be helpful to know at which arterial blood pressure terminal cardiovascular collapse occurs. METHODS: In this retrospective cohort study, we aimed to identify the arterial blood pressure associated with terminal cardiovascular collapse in 140 patients who died in the intensive care unit while being invasively monitored. Demographic data, co-morbid conditions and clinical data at admission and during the 24 hours before and at the time of terminal cardiovascular collapse were collected. The systolic, mean and diastolic arterial blood pressures immediately before terminal cardiovascular collapse were documented. Terminal cardiovascular collapse was defined as an abrupt (<5 minutes) and exponential decrease in heart rate (> 50% compared to preceding values) followed by cardiac arrest. RESULTS: The mean ± standard deviation (SD) values of the systolic, mean and diastolic arterial blood pressures associated with terminal cardiovascular collapse were 47 ± 12 mmHg, 35 ± 11 mmHg and 29 ± 9 mmHg, respectively. Patients with congestive heart failure (39 ± 13 mmHg versus 34 ± 10 mmHg; P = 0.04), left main stem stenosis (39 ± 11 mmHg versus 34 ± 11 mmHg; P = 0.03) or acute right heart failure (39 ± 13 mmHg versus 34 ± 10 mmHg; P = 0.03) had higher arterial blood pressures than patients without these risk factors. Patients with severe valvular aortic stenosis had the highest arterial blood pressures associated with terminal cardiovascular collapse (systolic, 60 ± 20 mmHg; mean, 46 ± 12 mmHg; diastolic, 36 ± 10 mmHg), but this difference was not significant. Patients with sepsis and patients exposed to sedatives or opioids during the terminal phase exhibited lower arterial blood pressures than patients without sepsis or administration of such drugs. CONCLUSIONS: The arterial blood pressure associated with terminal cardiovascular collapse in critically ill patients was very low and varied with individual co-morbid conditions (for example, congestive heart failure, left main stem stenosis, severe valvular aortic stenosis, acute right heart failure), drug exposure (for example, sedatives or opioids) and the type of acute illness (for example, sepsis).

On sepsis, troponin and vasopressin: the bitter truth.

One of the rationales for the use of vasopressin in septic shock has been its potential cardioprotective mechanisms. Lower heart rates, higher arterial pressures, and fewer norepinephrine doses during vasopressin therapy were hypothesized to protect the heart from myocardial ischemia. In a prospective sub-study of the VASST (Vasopressin in Septic Shock Trial) project, Mehta and colleagues specifically evaluated this hypothesis but failed to find lower cardiac biomarkers or fewer ischemic electrocardiogram changes in patients receiving vasopressin compared with subjects receiving norepinephrine alone. After recent evidence of a lacking survival benefit, the present study results further challenge the future role of vasopressin as a vasopressor in septic shock.

Rate and pattern of antibiotic resistance in microbiological cultures of sepsis patients in a low-middle-income country's ICU.

BACKGROUND: In this prospective, observational study, the rate of antibiotic resistance in cultures sampled from sepsis patients was determined in an intensive care unit of a low-middle income country. METHODS: Critically ill patients suffering from bacterial sepsis were eligible for enrollment. Aside from demographic, disease-related and sepsis-specific parameters, the type of microbiological sample and cultured microorganism as well as the resistance pattern (extensively resistant bacteria, multi-drug resistant bacteria) were documented. Descriptive statistical methods, parametric and non-parametric tests were used. RESULTS: 215 sepsis patients were included. 193 ofthe 410 cultured organisms (47.1%) showed antibiotic resistance [extensively resistant bacteria, n = 90 (11%); multi-drug resistant bacteria, n = 103 (25.1%)]. 51.6% of the patients were infected by > or = 1 resistant bacteria. Bacteria with an exceptionally high rate of antibiotic resistance were Acinetobacter baumannii (90%), Enterobacter spp (60%) and coagulase-negative Staphylococci (60%). Patients infected with resistant bacteria more often received inadequate empirical antibiotic therapy (36.9 vs. 13.5%, p < 0.001), required mechanical ventilation (66.7 vs. 42.3%, p < 0.001) and renal replacement therapy (28.8 vs. 9.6%, p < 0.001) more frequently, and had a longer stay in the intensive care unit [5 (3-9.5) vs. 5 (2-8)%, p < 0.001] than patients with sepsis due to non-resistant bacteria. There was a trend towards a higher mortality in patients with resistant bacteria (43.2 vs. 31.7%, p = 0.09). CONCLUSION: Resistant bacteria were detected in up to 50% of microbiological samples from critically ill sepsis patients in the intensive care unit of a low-middle-income country. Antibiotic resistance appears to be a relevant problem of sepsis management in a resource-limited setting.

High CRP Levels After Critical Illness are Associated With an Increased Risk of Rehospitalization.

PURPOSE: Chronic inflammation, even at subclinical levels, is associated with adverse long-term outcome. PATIENTS AND METHODS: In this prospective, observational study, 66 critically ill patients surviving to hospital discharge were included. C-reactive protein (CRP) levels were determined at hospital discharge, 1, 2, and 6 weeks after hospital discharge. All the patients were repeatedly screened for adverse events resulting in rehospitalization or death for 1.5 years. RESULTS: After hospital discharge, over two-thirds of the patients exhibited elevated CRP levels (>2.0 mg/L). During the first week, CRP decreased compared with hospital discharge (P < 0.001) but did not change after week 1 (P = 0.67). Age (P = 0.24), surgical status (P = 0.95), or sepsis (P = 0.77) did not influence the CRP course. The latter differed between patients with (n = 15) and without (n = 51) adverse events (P = 0.003). CRP levels of patients without adverse events persistently decreased after hospital discharge (P = 0.03), whereas those of patients with adverse events did not (P = 0.86) but rebounded early. CONCLUSIONS: Plasma CRP levels in critically ill patients decreased during the first week after hospital discharge but remained unchanged during the subsequent 5 weeks. Over two-thirds of the patients exhibited elevated CRP levels compatible with chronic sub-clinical inflammation. Persistently elevated CRP levels after hospital discharge are associated with higher risk of rehospitalization.

Changes in peripheral perfusion relate to visceral organ perfusion in early septic shock: A pilot study.

PURPOSE: To correlate clinical indicators of peripheral perfusion with visceral organ vascular tone in 30 septic shock patients. MATERIALS AND METHODS: In a prospective pilot study, capillary refill time, the Mottling score, and peripheral temperature were determined within 24, 48, and 72 hours after intensive care unit admission. Simultaneously, pulsatility indices in the liver, spleen, kidneys, and intestines were measured by Doppler ultrasonography. Correlation analyses were calculated, applying an adjusted significance level (P< .0125) to correct for multiple testing. RESULTS: Significant relationships were observed between the pulsatility index of selected organs and the capillary refill time (intestines: r= 0.325, P= .007), and the Mottling score (kidneys: r= 0.396, P= .006), but not peripheral temperature (all r< 0.14, P> .05). An association over time was observed for the capillary refill time and pulsatility index of the liver (P= .04) and intestines (P= .03) as well as for the Mottling score and the kidneys' pulsatility index (P= .03), but not for peripheral temperature and any visceral organs' pulsatility index. CONCLUSIONS: Capillary refill time and skin mottling may be correlated with the pulsatility index, a sonographic surrogate of vascular tone, of visceral organs in early septic shock.

Prolonged bilateral reactive miosis as a symptom of severe insulin intoxication.

BACKGROUND: Miosis occurs following exposure to toxins that decrease the sympathomimetic tone, increase the cholinergic tone, or exert sedative-hypnotic effects, but has not been reported in insulin poisoning. CASE REPORT: A 64-year- old woman without co-morbidities was found unconscious next to an empty insulin pen. Her Glasgow Coma Scale was 3 with absent reflexes, bilateral reactive miosis, and injection marks across the abdominal wall. The patient was endotracheally intubated, mechanically ventilated, and transferred to this hospital. At admission, the blood glucose level was 34 mg/dL. Glasgow Coma Scale remained at 3, with persistent bilateral reactive miosis. The toxicology screening was negative for ethanol, barbiturates, tricyclic antidepressants, phenothiazines, amphetamines, cannabinoids, salicylates, acetaminophen, and cocaine. Cranial computed tomography with angiography and magnetic resonance imaging (MRI) did not show any structural brain lesions. Intravenous glucose was continued at 6-14 g/h for 3 days. On repeated neurological examinations, the patient remained deeply comatose, with partial loss of cranial nerve function. Bilateral reactive miosis persisted for 4 days. From day 5 on, the patient awoke progressively. At discharge, the patient was fully alert and orientated, without a focal neurological deficit. CONCLUSIONS: Prolonged bilateral reactive miosis can be a clinical symptom accompanying metabolic encephalopathy in severe insulin poisoning. Functional impairment of the pons due to relative hypoperfusion during hypoglycemia may serve as a reasonable pathophysiologic explanation for this phenomenon.

Renal replacement therapy with regional citrate anticoagulation as an effective method to treat hypercalcemic crisis.

Hemodialysis is considered the renal replacement technique of choice to control life-threatening hypercalcemia. In this case series, the experience with continuous venovenous hemodiafiltration (CVVHDF) with regional citrate anticoagulation to control five hypercalcemic crises in four patients is summarized. Overall maximum ionized and total calcium levels ranged from 1.72 to 2.01 mmol/L and 3.1 to 4.2 mmol/L, respectively. All patients presented with impaired consciousness, cardiac arrhythmias, or acute oliguria, despite therapy. Trisodium citrate was administered at 3 mmol/h (hourly calcium replacement 1.15-2.75 mmol). This allowed a controlled decrease in ionized calcium levels below 1.4 mmol/L within 4 hours (interquartile range [IQR], 2.5-10) and resolution of neurological symptoms within 15.5 hours (IQR, 12-22.8). The duration of CVVHDF was 1 day in those patients in whom hypercalcemia was the reason for admission. Four asymptomatic episodes of mild hypocalcemia occurred in two patients. No patient developed relevant abnormalities of serum sodium levels or pH, experienced cardiac arrhythmia, or required transfusion of blood products during CVVHDF. One patient with metastatic bronchial carcinoma experienced rebound hypercalcemic crisis 13 days after a 1 day session of CVVHDF with regional citrate anticoagulation. In conclusion, CVVHDF with regional citrate anticoagulation appears to be effective and potentially safe to rapidly normalize calcium levels in hypercalcemic crisis.

Influence of in-line microfilters on systemic inflammation in adult critically ill patients: a prospective, randomized, controlled open-label trial.

BACKGROUND: In critically ill children, in-line microfilters may reduce the incidence of the systemic inflammatory response syndrome (SIRS), the overall complication and organ dysfunction rate. No data on the use of in-line microfilters exist in critically ill adults. METHODS: In this prospective, randomized, controlled open-label study, we evaluated the influence of in-line microfilters on systemic immune activation in 504 critically ill adults with a central venous catheter in place and an expected length of stay in the intensive care unit >24 h. Patients were randomized to have in-line microfilters placed into all intravenous lines (intervention group) or usual care (control group). The primary endpoint was the number of intensive care unit days with SIRS. Secondary endpoints were the incidence of SIRS, SIRS criteria per day, duration of invasive mechanical ventilation, intensive care unit length of stay, the incidence of acute lung injury, maximum C-reactive protein, maximum white blood cell count, incidence of new candida and/or central-line-associated bloodstream infections, incidence of new thromboembolic complications, cumulative insulin requirements and presence of hyper- or hypoglycemia. RESULTS: The study groups did not differ in any baseline variable. There was no difference in the number of days in the intensive care unit with SIRS between microfilter and control patients [2 (0.8-4.7) vs. 1.8 (0.7-4.4), p = 0.62]. Except for a higher incidence of SIRS in microfilter patients (99.6 vs. 96.8 %, p = 0.04), no difference between the groups was observed in any secondary outcome parameter. Results did not change when only patients with an intensive care unit length of stay of greater than 7 days were included in the analysis. The rate of adverse events was comparable between microfilter and control patients. In two patients allocated to the microfilter group, the study intervention was discontinued for technical reasons. Use of in-line microfilters was associated with additional costs. CONCLUSIONS: The use of in-line microfilters failed to modulate systemic inflammation and clinical outcome parameters in critically ill adults. TRIAL REGISTRATION: Clinical Trials NCT01534390.

Fulminant systemic capillary leak syndrome due to C1 inhibitor deficiency complicating acute dermatomyositis: a case report.

INTRODUCTION: Dermatomyositis is a chronic inflammatory disorder characterized by muscular and dermatologic symptoms with variable internal organ involvement. This is the first report on a patient with acute dermatomyositis and fulminant systemic capillary leak syndrome. CASE PRESENTATION: A 69-year-old Caucasian woman with chronic dermatomyositis presented with clinical signs of severe hypovolemic shock and pronounced hemoconcentration (hematocrit, 69%). Her colloid osmotic pressure was 4.6mmHg. Following a bolus dose of prednisolone (500mg), fluid resuscitation was initiated. During volume loading, anasarca and acute respiratory distress rapidly developed. Echocardiography revealed an underfilled, hypokinetic, diastolic dysfunctional left ventricle with pericardial effusion but no signs of tamponade. Despite continued fluid resuscitation and high-dosed catecholamine therapy, the patient died from refractory shock 12 hours after intensive care unit admission. A laboratory analysis of her complement system suggested the presence of C1 inhibitor deficiency as the cause for systemic capillary leakage. The post-mortem examination revealed bilateral pleural, pericardial and peritoneal effusions as well as left ventricular hypertrophy with patchy myocardial fibrosis. Different patterns of endomysial/perimysial lymphocytic infiltrations adjacent to degenerated cardiomyocytes in her myocardium and necrotic muscle fibers in her right psoas major muscle were found in the histological examination. CONCLUSIONS: This case report indicates that acute exacerbation of chronic dermatomyositis can result in a fulminant systemic capillary leak syndrome with intense hemoconcentration, hypovolemic shock and acute heart failure. In the presented patient, the cause for diffuse capillary leakage was most probably acquired angioedema, a condition that has been associated with both lymphoproliferative and autoimmunologic disorders.