David Konrad

A controlled trial of electronic automated advisory vital signs monitoring in general hospital wards

Objectives: Deteriorating ward patients are at increased risk. Electronic automated advisory vital signs monitors may help identify such patients and improve their outcomes. Setting: A total of 349 beds, in 12 general wards in ten hospitals in the United States, Europe, and Australia. Patients: Cohort of 18,305 patients. Design: Before-and-after controlled trial. Intervention: We deployed electronic automated advisory vital signs monitors to assist in the acquisition of vital signs and calculation of early warning scores. We assessed their effect on frequency, type, and treatment of rapid response team calls; survival to hospital discharge or to 90 days for rapid response team call patients; overall type and number of serious adverse events and length of hospital stay. Measurements and Main Results: We studied 9,617 patients before (control) and 8,688 after (intervention) deployment of electronic automated advisory vital signs monitors. Among rapid response team call patients, intervention was associated with an increased proportion of calls secondary to abnormal respiratory vital signs (from 21% to 31%; difference [95% confidence interval] 9.9 [0.1–18.5]; p = .029). Survival immediately after rapid response team treatment and survival to hospital discharge or 90 days increased from 86% to 92% (difference [95% confidence interval] 6.3 [0.0–12.6]; p = .04). Intervention was also associated with a decrease in median length of hospital stay in all patients (unadjusted p < .0001; adjusted p = .09) and more so in U.S. patients (from 3.4 to 3.0 days; unadjusted p < .0001; adjusted ratio [95% confidence interval] 1.03 [1.00–1.06]; p = .026). The time required to complete and record a set of vital signs decreased from 4.1 ± 1.3 mins to 2.5 ± 0.5 mins (difference [95% confidence interval] 1.6 [1.4–1.8]; p < .0001). Conclusions: Deployment of electronic automated advisory vital signs monitors was associated with an improvement in the proportion of rapid response team-calls triggered by respiratory criteria, increased survival of patients receiving rapid response team calls, and decreased time required for vital signs measurement and recording (NCT01197326).

Effects of levosimendan, a novel inotropic calcium-sensitizing drug, in experimental septic shock.

Objective Levosimendan is a novel inodilator that improves cardiac contractility by sensitizing troponin C to calcium. This drug has proved to be effective in treating advanced congestive heart failure but has not been evaluated in septic settings. The purpose of the present study was to study the effects of this drug in a porcine model of endotoxemia. Design Prospective experimental study. Subjects Fourteen landrace pigs. Interventions All animals were anesthetized and catheterized for measurement of central and pulmonary hemodynamics. Ultrasonic flow probes were placed around the renal artery and portal vein to measure blood flow. A tonometer was placed in the ileum to measure mucosal pH. Levosimendan was given to six animals as a bolus (200 &mgr;g·kg−1) followed by a continuous infusion (200 &mgr;g·kg−1· hr−1). Thirty minutes after onset of levosimendan treatment, all animals received endotoxin (20 &mgr;g·kg−1·hr−1 for 3 hrs). Measurements and Main Results At baseline, levosimendan induced a systemic vasodilation with a reduction in blood pressure and an increase in heart rate. A tendency to an increase in cardiac index did not reach statistical significance (p = .055).Cardiac index and systemic oxygen delivery were markedly improved in the levosimendan group during endotoxemia. Systemic vascular resistance and blood pressure were reduced in the levosimendan group. The latter parameter, however, was only different from the control group during the initial phase of endotoxin shock but not at the late, most pronounced phase of shock. Levosimendan also efficiently attenuated endotoxin-induced pulmonary hypertension. Portal venous blood flow and gut oxygen delivery were improved, but no concomitant reduction in endotoxin-induced intestinal mucosal acidosis was observed. Renal blood flow was unaffected, as was the endotoxin-induced increase in plasma endothelin-1-like immunoreactivity.These findings support previous reports of calcium desensitization as a potential component in septic myocardial depression. Furthermore, the vasodilatory properties of this drug were well tolerated in the current model of hypodynamic endotoxin shock, and they may have contributed to improved regional blood flow as seen in the gut as well as improved systemic perfusion by means of reduced biventricular afterload. Conclusion Pretreatment with levosimendan in pigs subjected to endotoxin shock improved cardiac output and systemic and gut oxygen delivery. In addition, pulmonary hypertension largely was attenuated without any adverse effects on gas exchange. These results are promising in several aspects, but the role of levosimendan in the treating circulatory failure in sepsis remains to be established.

Comparison of a single indicator and gravimetric technique for estimation of extravascular lung water in endotoxemic pigs

Objectives:To compare the single thermal indicator dilution (STID) technique for measurement of extravascular lung water (EVLWSTID) with gravimetrically determined EVLW (EVLWGRAV) in anesthetized pigs under sham and endotoxemic conditions. Design:Open experimental comparative animal study. Setting:University animal research laboratory. Subjects:Fifteen anesthetized landrace pigs. Interventions:Endotoxin infusion during 5 hrs in five pigs. Six animals were only anesthetized and rested for 5 hrs. In four additional animals, the impact on EVLWSTID measurements by changes in pulmonary perfusion, ventilation, and the combination of the two was studied. The alterations in ventilation and perfusion were induced by caval balloon inflation, inflation of the pulmonary artery catheter balloon, and bronchial plugging respectively. Measurements and Main Results:The STID technique, with default settings of the intrathoracic blood volume (ITBV) to global end-diastolic volume (GEDV) (i.e., the extrapulmonary intravascular volume between the point of injection of the indicator, and the point of detection) relationship (ITBV = 1.25GEDV), systematically overestimated the EVLW index compared with the gravimetrical method (mean bias of 5.4 mL/kg). By adapting the ITBV to GEDV relationship to the current model (ITBV = 1.52GEDV + 49.7), the accuracy of the STID technique improved. Moreover, the measurement of EVLWSTID proved to be reduced by manipulation of pulmonary perfusion and ventilation. However, the STID technique could detect an increase in EVLW during endotoxemia independent of the ITBV/GEDV relationship used. Conclusion:Despite technological improvement, the dilution techniques for the measurement of EVLW might still be influenced by changes in perfusion and ventilation. The STID technique, in addition, might demand adjustment of the ITBV/GEDV relationship to the particular condition and species subjected to measurement. The STID technique may, however, be a useful tool for monitoring changes of EVLW over time, but further studies are warranted to confirm this.

Emergency and critical care services in Tanzania: a survey of ten hospitals

BackgroundWhile there is a need for good quality care for patients with serious reversible disease in all countries in the world, Emergency and Critical Care tends to be one of the weakest parts of health systems in low-income countries. We assessed the structure and availability of resources for Emergency and Critical Care in Tanzania in order to identify the priorities for improving care in this neglected specialty.MethodsTen hospitals in four regions of Tanzania were assessed using a structured data collection tool. Quality was evaluated with standards developed from the literature and expert opinion.ResultsImportant deficits were identified in infrastructure, routines and training. Only 30% of the hospitals had an emergency room for adult and paediatric patients. None of the seven district and regional hospitals had a triage area or intensive care unit for adults. Only 40% of the hospitals had formal systems for adult triage and in less than one third were critically ill patients seen by clinicians more than once daily. In 80% of the hospitals there were no staff trained in adult triage or critical care. In contrast, a majority of equipment and drugs necessary for emergency and critical care were available in the hospitals (median 90% and 100% respectively. The referral/private hospitals tended to have a greater overall availability of resources (median 89.7%) than district/regional hospitals (median 70.6).ConclusionsMany of the structures necessary for Emergency and Critical Care are lacking in hospitals in Tanzania. Particular weaknesses are infrastructure, routines and training, whereas the availability of drugs and equipment is generally good. Policies to improve hospital systems for the care of emergency and critically ill patients should be prioritised.

Differentiated and dose-related cardiovascular effects of a dual endothelin receptor antagonist in endotoxin shock.

Objective:To evaluate the effects of endothelin receptor antagonism on cardiac performance in endotoxin shock. Design:Prospective, experimental study. Setting:A university-affiliated research institution. Subjects:Domestic anesthetized landrace pigs. Interventions:Thirty-seven pigs were anesthetized and subjected to echocardiography, coronary sinus catheterization, and monitoring of central and regional hemodynamics in order to assess cardiac performance. All animals received endotoxin for 5 hrs. Twenty pigs served as endotoxin controls. Tezosentan, a dual endothelin-A and -B receptor antagonist, was administered during established endotoxemic shock. Seven pigs received an infusion of tezosentan of 1·mg·kg−1·hr−1 (tezo1), and an additional ten pigs received a higher dose of 10 mg·kg−1·hr−1 (tezo10). Measurements and Main Results:Endotoxemia evoked a state of shock with pulmonary hypertension and metabolic acidosis. A decrease in stroke volume and coronary perfusion pressure as well as an increase in troponin I was also noted. Tezosentan administration resulted in a significant increase in cardiac index, stroke volume index, left ventricular stroke work index, and left ventricular end-diastolic area index. Decreases in systemic and pulmonary vascular resistance indexes were also evident after intervention. This was achieved without changes in heart rate or systemic arterial or pulmonary artery occlusion pressures in tezo1 animals compared with controls. In addition, metabolic variables were improved by tezosentan. These effects were sustained only in the tezo1 group. In the higher dosage, tezosentan resulted in a deterioration of cardiac performance and 50% mortality rate. The endotoxin-induced increase in troponin I was attenuated in the tezo1 group compared with controls. Conclusions:In this porcine model of volume-resuscitated, endotoxemic shock, endothelin-receptor blockade with tezosentan improved cardiac performance. However, the effect was not sustained with higher doses of tezosentan, possibly due to reduced coronary perfusion pressure. These findings show differentiated, dose-dependent effects by dual endothelin receptor blockade on endotoxin-induced cardiovascular dysfunction.

Tezosentan counteracts endotoxin-induced pulmonary edema and improves gas exchange

Sepsis-induced acute lung injury is still associated with high morbidity and mortality. The pathophysiology is complex, and markers of injury include increased extravascular lung water. To evaluate the effects of the novel dual endothelin receptor antagonist tezosentan on endotoxin-induced changes in extravascular lung water and gas exchange, 16 pigs were anaesthetized and catheterized. Twelve animals were subjected to 5 h of endotoxemia. After 2 h, six of these animals received a bolus of tezosentan 1 mg kg−1 followed by a continuous infusion of 1 mg kg−1 h−1 to the end of the experiment at 5 h. Conventional pulmonary and hemodynamic parameters were measured. Extravascular lung water was determined in these pigs after 5 h of endotoxemia, as well as in the four additional nonendotoxemic sham animals. Tezosentan in the current dosage counteracted the deterioration of lung function caused by endotoxin, as measured by dead space, venous admixture, and compliance. In addition, pulmonary hypertension was attenuated. Tezosentan had a marked effect on the endotoxin-induced increase in extravascular lung water that was reduced to levels observed in nonendotoxemic sham animals. These results suggest that endothelin is involved in endotoxin-induced lung injury and the development of pulmonary edema. Dual endothelin receptor antagonism may be of value in the treatment of sepsis-related acute lung injury.

ICU admittance by a rapid response team versus conventional admittance, characteristics, and outcome.

Objective:To evaluate characteristics and outcome of ICU patients admitted from general wards based on mode of admittance, via a rapid response team or conventional contact. Design:Observational prospective study. Setting:General ICU of a university hospital. Patients:A total of 694 admissions to ICU from general wards. Interventions:None. Measurements and Main Results:Between 2007 and 2009, two cohorts admitted to ICU from general wards were identified: those admitted by the rapid response team and those admitted in a conventional way. Patients admitted directly from the trauma room, the emergency department, operating room, other hospitals, or other ICUs were excluded. Of 694 admissions, 355 came through a rapid response team call. Rapid response team patients were older (p < 0.01), and they had more severe comorbidities, higher severity score (p < 0.01), and almost three times more often the diagnosis of severe sepsis (p < 0.01) than conventionally admitted patients. Rapid response team patients had higher ICU mortality and 30-day mortality with a crude odds ratio for mortality within 30 days of 1.57 (95% confidence interval 1.08–2.28). Adjusted for age and comorbidities however, the difference was no longer significant with an odds ratio of 1.11 (95% confidence interval 0.70–1.76). Conclusions:This study suggests that the rapid response team is an important system for identifying complex patients in need of intensive care. More than half of ICU admissions from the wards came through a rapid response team call. Compared with conventional admissions, rapid response team patients had a high proportion of characteristics that could be related to a worse prognosis. Severe sepsis at the wards was mainly detected by the rapid response team and was the most common admitting diagnosis among the rapid response team patients. When adjusted for confounding factors, outcome between the groups did not differ, supporting the use of rapid response systems to identify deteriorating ward patients.

Single Deranged Physiologic Parameters Are Associated With Mortality in a Low-Income Country

Objective:To investigate whether deranged physiologic parameters at admission to an ICU in Tanzania are associated with in-hospital mortality and compare single deranged physiologic parameters to a more complex scoring system. Design:Prospective, observational cohort study of patient notes and admission records. Data were collected on vital signs at admission to the ICU, patient characteristics, and outcomes. Cutoffs for deranged physiologic parameters were defined a priori and their association with in-hospital mortality was analyzed using multivariable logistic regression. Setting:ICU at Muhimbili National Hospital, Dar es Salaam, Tanzania. Patients:All adults admitted to the ICU in a 15-month period. Measurements and Main Results:Two hundred sixty-nine patients were included: 54% female, median age 35 years. In-hospital mortality was 50%. At admission, 69% of patients had one or more deranged physiologic parameter. Sixty-four percent of the patients with a deranged physiologic parameter died in hospital compared with 18% without (p < 0.001). The presence of a deranged physiologic parameter was associated with mortality (adjusted odds ratio, 4.64; 95% CI, 1.95–11.09). Mortality increased with increasing number of deranged physiologic parameters (odds ratio per deranged physiologic parameter, 2.24 [1.53–3.26]). Every individual deranged physiologic parameter was associated with mortality with unadjusted odds ratios between 1.92 and 16.16. A National Early Warning Score of greater than or equal to 7 had an association with mortality (odds ratio, 2.51 [1.23–5.14]). Conclusion:Single deranged physiologic parameters at admission are associated with mortality in a critically ill population in a low-income country. As a measure of illness severity, single deranged physiologic parameters are as useful as a compound scoring system in this setting and could be termed “danger signs.” Danger signs may be suitable for the basis of routines to identify and treat critically ill patients.

Vital Signs Directed Therapy: Improving Care in an Intensive Care Unit in a Low-Income Country

Background Global Critical Care is attracting increasing attention. At several million deaths per year, the worldwide burden of critical illness is greater than generally appreciated. Low income countries (LICs) have a disproportionally greater share of critical illness, and yet critical care facilities are scarce in such settings. Routines utilizing abnormal vital signs to identify critical illness and trigger medical interventions have become common in high-income countries but have not been investigated in LICs. The aim of the study was to assess whether the introduction of a vital signs directed therapy protocol improved acute care and reduced mortality in an Intensive Care Unit (ICU) in Tanzania. Methods and Findings Prospective, before-and-after interventional study in the ICU of a university hospital in Tanzania. A context-appropriate protocol that defined danger levels of severely abnormal vital signs and stipulated acute treatment responses was implemented in a four week period using sensitisation, training, job aids, supervision and feedback. Acute treatment of danger signs at admission and during care in the ICU and in-hospital mortality were compared pre and post-implementation using regression models. Danger signs from 447 patients were included: 269 pre-implementation and 178 post-implementation. Acute treatment of danger signs was higher post-implementation (at admission: 72.9% vs 23.1%, p<0.001; in ICU: 16.6% vs 2.9%, p<0.001). A danger sign was five times more likely to be treated post-implementation (Prevalence Ratio (PR) 4.9 (2.9–8.3)). Intravenous fluids were given in response to 35.0% of hypotensive episodes post-implementation, as compared to 4.1% pre-implementation (PR 6.4 (2.5–16.2)). In patients admitted with hypotension, mortality was lower post-implementation (69.2% vs 92.3% p = 0.02) giving a numbers-needed-to-treat of 4.3. Overall in-hospital mortality rates were unchanged (49.4% vs 49.8%, p = 0.94). Conclusion The introduction of a vital signs directed therapy protocol improved the acute treatment of abnormal vital signs in an ICU in a low-income country. Mortality rates were reduced for patients with hypotension at admission but not for all patients.

Comparison of gravimetric and a double-indicator dilution technique for assessment of extra-vascular lung water in endotoxaemia

Objective. To compare a molecular double-indicator dilution technique with the gravimetrical reference method for measurement of extra-vascular lung water in porcine endotoxin shock.Design. Open comparative experimental study.Setting. Animal research laboratory.Measurements and results. In fourteen anaesthetised, mechanically ventilated landrace pigs, central and pulmonary haemodynamics as well as pulmonary gas exchange were measured. Extra-vascular lung water was quantitated gravimetrically as well as with a molecular double indicator dilution technique. Eight of these animals were subjected to endotoxaemia, the rest serving as sham controls. No difference in extra-vascular lung water was observed between the two methods in sham animals. Furthermore, extra-vascular lung water assessed with the molecular double-indicator dilution technique at the initiation of endotoxin infusion did not differ significantly from the corresponding values for sham animals. Endotoxaemia induced a hypodynamic shock with concurrent pulmonary hypertension and a pronounced deterioration in gas exchange. No increase in extra-vascular lung water was detected with the molecular double-indicator dilution technique in response to endotoxin, whereas this parameter was significantly higher when assessed with the gravimetric method.Conclusion. The molecular double-indicator dilution technique showed similar results as the gravimetrical method for assessment of extra-vascular lung water in non-endotoxaemic conditions. However, during endotoxin-induced lung injury the molecular double indicator dilution technique failed to detect the significant increase in extra-vascular lung water as measured by the gravimetric method. These data suggest that the molecular double indicator dilution technique may be of limited value during sepsis-induced lung injury.