Risk factors and outcomes of chronic opioid use following trauma.

BACKGROUND: The growing problem of opioid misuse has become a serious crisis in many countries. The role of trauma as a gateway to opioid use is currently not determined. The study was undertaken to assess whether traumatic injury might be associated with chronic opioid use and accompanying increased long-term mortality. METHODS: Injured patients and controls from Sweden were matched for age, sex and municipality. After linkage to Swedish health registers, opioid consumption was assessed before and after trauma. Among injured patients, logistic regression was used to investigate factors associated with chronic opioid use, assessed by at least one written and dispensed prescription in the second quarter after trauma. Cox regression was employed to study excess risk of mortality. In addition, causes of death for postinjury opioid users were explored. RESULTS: Some 13 309 injured patients and 70 621 controls were analysed. Exposure to trauma was independently associated with chronic opioid use (odds ratio 3·28, 95 per cent c.i. 3·02 to 3·55); this use was associated with age, low level of education, somatic co-morbidity, psychiatric co-morbidity, pretrauma opioid use and severe injury. The adjusted hazard ratio for death from any cause 6-18 months after trauma for chronic opioid users was 1·82 (95 per cent c.i. 1·34 to 2·48). Findings were similar in a subset of injured patients with no pretrauma opioid exposure. CONCLUSION: Traumatic injury was associated with chronic opioid use. These patients have an excess risk of death in the 6-18 months after trauma.

ANTECEDENTES: El uso indebido de opioides es un problema creciente que se ha convertido en una grave crisis en muchos países. No se ha analizado el papel de las lesiones traumáticas como puerta de entrada al uso de opioides. Se estableció la hipótesis de que una lesión traumática podría asociarse con el uso crónico de opioides y acompañarse de un aumento de la mortalidad a largo plazo. MÉTODOS: Se ajustaron por edad, sexo y municipio a los pacientes suecos con lesiones traumáticas y sus controles. Después de vincular varios registros de salud suecos, se evaluó el consumo de opioides antes y después de la lesión traumática. En los pacientes con lesiones traumáticas, se utilizó una regresión logística para definir los factores asociados con el uso crónico de opioides, definida como una receta prescrita y dispensada en el segundo trimestre después de la lesión traumática, y ​​una regresión de Cox para estudiar el exceso de riesgo de mortalidad. Además, se exploraron las causas de muerte de los usuarios de opioides postraumáticos. RESULTADOS: Se analizaron 13.309 pacientes con lesiones traumáticas y 70.621 controles. La exposición a una lesión traumática se asoció de forma independiente con el uso crónico de opioides, (razón de oportunidades, odds ratio, OR) OR 3,3 (i.c. del 95% 3,0-3,6), y dicho uso se asoció con la edad, el bajo nivel educativo, las comorbilidad físicas y psiquiátricas, el uso previo de opioides y la gravedad de las lesiones. El cociente de riesgos instantáneos, hazard ratio, HR ajustado de muerte por cualquier causa a los 6-18 meses de la lesión traumática para los consumidores crónicos de opioides fue de 1,8 (i.c. del 95% 1,3-2,5). En un subconjunto de pacientes con lesiones traumáticas sin exposición previa a los opioides, los hallazgos fueron similares. CONCLUSIÓN: La lesión traumática se asoció con el uso crónico de opioides. Estos pacientes presentan un exceso de riesgo de mortalidad entre los 6 y 8 meses después del trauma.

Effect of preadmission beta-blockade on mortality in multiple trauma.

BACKGROUND: High levels of circulating catecholamines after multiple trauma have been associated with increased morbidity and mortality. Beta-adrenergic receptor antagonist (beta-blocker) therapy has emerged as a potential treatment option, but the effect of preinjury beta-blockade on trauma-induced mortality is unclear. The aim of this study was to assess whether preinjury beta-blocker therapy is associated with reduced mortality after multiple trauma. METHODS: Severely injured patients, aged at least 50 years, admitted to a level one trauma centre over a 10-year interval were linked to national and local registries of co-morbidities, prescription drug use and level of education. The association between preinjury beta-blocker use and 30-day mortality was explored using logistic regression analysis. RESULTS: Some 1376 patients were included; 338 (24·6 per cent) were receiving beta-blockers at the time of trauma. Beta-blocker users had an increased crude 30-day mortality rate compared with that for non-users: 32·8 versus 19·7 per cent respectively (P < 0·001). After adjustment for baseline imbalances and injury-related factors, there was no association between preinjury beta-blocker use and mortality (OR 1·09, 95 per cent c.i. 0·70 to 1·70). Separate analyses of individuals with or without severe head injury did not significantly change this association. There was no significant difference in the rate of shock between beta-blocker users and non-users. CONCLUSION: Pretrauma beta-blockade is not associated with 30-day mortality beyond the effects of age, co-morbidity and injury severity.

Heparin-binding protein as a biomarker of post-injury sepsis in trauma patients.

BACKGROUND: Heparin-binding protein (HBP) is a neutrophil-derived protein advocated as a biomarker in sepsis. We evaluated plasma HBP as a predictor of post-injury sepsis in trauma patients. METHODS: Ninety-seven trauma patients were studied during the first week of intensive care. Injury-related data were collected and clinical parameters registered daily. Plasma HBP was sampled on day 1, 3 and 5 after trauma and evaluated for associations with injury-related parameters and sepsis. The predictive properties of HBP were compared to C-reactive protein (CRP) and white blood cell count (WBC). RESULTS: Median Injury Severity Score was 33, one-third of the trauma patients received massive transfusion and a quarter was in shock on arrival. Overall 30-day mortality was 8%. Plasma HBP was significantly higher in severely injured patients and associated with shock on arrival, massive transfusions and organ failure. Septic patients had higher levels of HBP only on day 5. When evaluated for prediction of onset of sepsis during the two following days after plasma sampling by receiver operating characteristic (ROC) analyses, areas under the curves were non-significant for all time points. Similar patterns were seen for CRP and WBC. CONCLUSION: In trauma patients, HBP levels are related to severity of injury and organ dysfunction. Heparin-binding protein was weakly associated with sepsis and only at the later stage of the observation period of 1 week. Moreover, HBP showed poor discriminatory properties as an early biomarker of post-injury sepsis. Trauma-induced inflammation during the post-injury phase may blunt the sepsis-predictive performance of HBP.

Causes of excessive late death after trauma compared with a matched control cohort.

BACKGROUND: Studies on mortality following trauma have been restricted mainly to in-hospital or 30-day death. Mortality risk may be sustained several years after trauma, but the causes of late death have not been elucidated. The aim was to investigate mortality and analyse causes of late death after trauma. METHODS: All injured patients from a regional trauma registry with long-term follow-up were matched in a 1 : 5 ratio with uninjured controls by age, sex and municipality. By linkage to national registries, long-term mortality, causes of death and co-morbidity status were identified. Excess mortality was examined by calculating the all-cause mortality rate ratio (MRR). RESULTS: Among the trauma cohort of 7382 patients, 662 (9·0 per cent) died within 3 years after the index trauma; the 30-day mortality rate was 5·0 per cent. Compared with the control group (36 759 individuals), there was a sustained increase in mortality up to 3 years after trauma; the MRR was 2·88 (95 per cent c.i. 2·37 to 3·50) for days 31-365, 1·59 (1·24 to 2·04) for years 1-2 and 1·43 (1·06 to 1·92) for years 2-3. External causes, including new trauma, were far more common causes of late death in injured patients than in matched controls. CONCLUSION: Postinjury mortality is increased for several years after trauma. Excess mortality is largely attributed to recurrent trauma and other external causes of death.

Shock treatment in a cohort of Scandinavian intensive care units in 2014.

BACKGROUND: Shock is common in intensive care units, and treatment includes fluids, vasopressor and/or inotropic drugs, guided by hemodynamic monitoring. The aim of this study was to identify current practice for treatment of shock in Scandinavian intensive care units. METHODS: Seven-day inception cohort study in 43 intensive care units in Scandinavia. Patients ≥ 15 years old receiving more than 4 h of cardiovascular acting drug infusion were included. The use of fluids, vasopressor and inotropic drugs, type of monitoring, and target values were recorded. RESULTS: One hundred and seventy-one patients were included. At inclusion, 136/168 (81%) had received vasopressor and/or inotropic drug therapy for less than 24 h, and 143/171 (84%) had received volume loading before the onset of vasoactive drug treatment. Ringer's solution was given to 129/143 (90%) of patients and starches in 3/143 (2%) patients. Noradrenaline was the most commonly used cardiovascular acting drug, given in 168/171 (98%) of cases while dopamine was rarely used. Mean arterial pressure was considered the most important variable for hemodynamic monitoring. Invasive arterial blood pressure was monitored in 166/171 (97%) of patients, arterial pulse wave analysis in 11/171 (7%), and echocardiography in 50/171 (29%). CONCLUSION: In this survey, Ringer's solution and noradrenaline were the most common first-line treatments in shock. The use of starches and dopamine were rare. Almost all patients were monitored with invasive arterial blood pressure, but comprehensive hemodynamic monitoring was used only in a minority of patients.

A novel continuous capnodynamic method for cardiac output assessment in a porcine model of lung lavage.

BACKGROUND: We have evaluated a new method for continuous monitoring of effective pulmonary blood flow (COEPBF ), i.e. cardiac output (CO) minus intra-pulmonary shunt, during mechanical ventilation. The method has shown good trending ability during severe hemodynamic challenges in a porcine model with intact lungs. In this study, we further evaluate the COEPBF method in a model of lung lavage. METHODS: COEPBF was compared to a reference method for CO during hemodynamic and PEEP alterations, 5 and 12 cmH2 O, before and after repeated lung lavages in 10 anaesthetised pigs. Bland-Altman, four-quadrant and polar plot methodologies were used to determine agreement and trending ability. RESULTS: After lung lavage at PEEP 5 cmH2 O, the ratio of arterial oxygen partial pressure related to inspired fraction of oxygen significantly decreased. The mean difference (limits of agreement) between methods changed from 0.2 (-1.1 to 1.5) to -0.9 (-3.6 to 1.9) l/min and percentage error increased from 34% to 70%. Trending ability remained good according to the four-quadrant plot (concordance rate 94%), whereas mean angular bias increased from 4° to -16° when using the polar plot methodology. CONCLUSION: Both agreement and precision of COEPBF were impaired in relation to CO when the shunt fraction was increased after lavage at PEEP 5 cmH2 O. However, trending ability remained good as assessed by the four-quadrant plot, whereas the mean polar angle, calculated by the polar plot, was wide.

Heparin-binding protein (HBP/CAP37) - a link to endothelin-1 in endotoxemia-induced pulmonary oedema?

BACKGROUND: Vascular leakage and oedema formation are key components in sepsis. In septic patients, plasma levels of the vasoconstrictive and pro-inflammatory peptide endothelin-1 (ET-1) correlate with mortality. During sepsis, neutrophils release heparin-binding protein (HBP) known to increase vascular permeability and to be a promising biomarker of human sepsis. As disruption of ET-signalling in endotoxemia attenuates formation of oedema, we hypothesized that this effect could be related to decreased levels of HBP. To investigate this, we studied the effects of ET-receptor antagonism on plasma HBP and oedema formation in a porcine model of sepsis. In addition, to further characterize a potential endothelin/HBP interaction, we investigated the effects of graded ET-receptor agonist infusions. METHODS: Sixteen anesthetized pigs were subjected to 5 h of endotoxemia and were randomized to receive either the ET-receptor antagonist tezosentan or vehicle after 2 h. Haemodynamics, gas-exchange and lung water were monitored. In separate experiments, plasma HBP was measured in eight non-endotoxemic animals exposed to graded infusion of ET-1 or sarafotoxin 6c. RESULTS: Endotoxemia increased plasma ET-1, plasma HBP, and extravascular lung water. Tezosentan-treatment markedly attenuated plasma HBP and extravascular lung water, and these parameters correlated significantly. Tezosentan decreased pulmonary vascular resistance and increased respiratory compliance. In non-endotoxemic pigs graded ET-1 and sarafotoxin 6c infusions caused a dose-dependent increase in plasma HBP. CONCLUSIONS: ET-receptor antagonism reduces porcine endotoxin-induced pulmonary oedema and plasma levels of the oedema-promoting protein HBP. Moreover, direct ET-receptor stimulation distinctively increases plasma HBP. Together, these results suggest a novel mechanism by which ET-1 contributes to formation of oedema during experimental sepsis.

Novel continuous capnodynamic method for cardiac output assessment during mechanical ventilation.

BACKGROUND: It is important to be able to accurately monitor cardiac output (CO) during high-risk surgery and in critically ill patients. The invasiveness of the pulmonary artery catheter (PAC) limits its use, and therefore, new minimally invasive methods for CO monitoring are needed. A potential method is estimation of CO from endogenous carbon dioxide measurements, using a differentiated Fick's principle to determine effective pulmonary blood flow (EPBF). In this study, we aimed to validate a novel capnodynamic method (COEPBF) in a wide range of clinically relevant haemodynamic conditions. METHODS: COEPBF was studied in 10 pigs during changes in preload, afterload, CO increase, and bleeding. An ultrasonic flow probe around the pulmonary artery was used as reference method of CO determination. CO was also measured using a PAC thermodilution technique (COPAC). CO and other haemodynamic data were recorded before and during each intervention. Accuracy and precision and also the ability to track changes in CO were determined using Bland-Altman, four-quadrant plot and polar plot analysis. RESULTS: COEPBF and COPAC showed equally good agreement, with a tendency to overestimate CO (bias 0.2 and 0.3 litre min(-1), respectively). The overall percentage error was 47% for COEPBF and 49% for COPAC. The concordance for tracking CO changes was 97 and 95% for COEPBF and COPAC, respectively, with an exclusion zone of 15% and radial limits of ±30°. CONCLUSIONS: COEPBF showed reliable trending abilities, equivalent to COPAC. COEPBF and COPAC also showed low bias but high percentage errors. Further studies in animal models of lung injury and in high-risk surgery patients are warranted.

High incidence of post-injury pneumonia in intensive care-treated trauma patients.

INTRODUCTION: Trauma patients are susceptible to post-injury infections. We investigated the incidence, as well as risk factors for development of pneumonia in intensive care unit (ICU)-treated trauma patients. In addition, we report pathogens identified in patients that developed pneumonia. METHODS: The study cohort consisted of 322 trauma patients admitted to the ICU at a level-one trauma centre following initial resuscitation. Patients 15 years or older with an ICU stay of more than 24 h were included. We investigated pre-hospital and hospital parameters during the first 24 h after admission and their possible association with pneumonia within 10 days of ICU admission. RESULTS: Majority of the patients were male (78%) and the median age was 41 years. The overall degree of injury was high with a median Injury Severity Score (ISS) of 24. Overall 30-day mortality was 9%. Eighty-five (26%) patients developed pneumonia during their first 10 days in the ICU. Univariate logistic regression revealed that intubation in the field, shock, Glasgow Coma Scale (GCS) 3-8, major surgery within 24 h after admission, massive transfusion and ISS > 24 were all risk factors for subsequent development of pneumonia. In the multivariable model, only GCS 3-8 was identified as an independent risk factor. In 42 out of the 85 cases of pneumonia, the diagnosis was defined by significant growth of at least one pathogen where Enterobacteriaceae and Staphylococcus aureus were the most common. CONCLUSIONS: Pneumonia is a common complication among ICU-treated trauma patients. Reduced consciousness is an independent risk factor for development of pneumonia after severe injury.

Heparin-binding protein (HBP): an early marker of respiratory failure after trauma?

BACKGROUND: Trauma and its complications contribute to morbidity and mortality in the general population. Trauma victims are susceptible to acute respiratory distress syndrome (ARDS) and sepsis. Polymorphonuclear leucocytes (PMNs) are activated after trauma and there is substantial evidence of their involvement in the development of ARDS. Activated PMNs release heparin-binding protein (HBP), a granule protein previously shown to be involved in acute inflammatory reactions. We hypothesised that there is an increase in plasma HBP content after trauma and that the increased levels are related to the severity of the trauma or later development of severe sepsis and organ failure (ARDS). METHODS AND MATERIAL: We investigated HBP in plasma samples within 36 h from trauma in 47 patients admitted to a level one trauma centre with a mean injury severity score (ISS) of 26 (21-34). ISS, admission sequential organ failure assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded at admission. ARDS and presence of severe sepsis were determined daily during intensive care. RESULTS: We found no correlation between individual maximal plasma HBP levels at admission and ISS, admission SOFA or APACHE II. We found, however, a correlation between HBP levels and development of ARDS (P = 0.026, n = 47), but not to severe sepsis. CONCLUSION: HBP is a potential biomarker candidate for early detection of ARDS development after trauma. Further research is required to confirm a casual relationship between plasma HBP and the development of ARDS.

Gut microcirculatory and mitochondrial effects of hyperdynamic endotoxaemic shock and norepinephrine treatment.

BACKGROUND: Microcirculatory and mitochondrial dysfunction are important factors in the development of septic shock. In this study, we investigated the effects of fluid resuscitated endotoxaemic shock and norepinephrine treatment on intestinal microcirculation and mitochondrial function in sheep. METHODS: Eight anaesthetized sheep received an i.v. infusion of endotoxin. After 24 h, mean arterial pressure (MAP) was restored to baseline levels with a norepinephrine infusion. Five sheep served as sham experiments. Central and regional haemodynamics were monitored, and ileal microcirculation was evaluated with laser Doppler and sidestream dark-field videomicroscopy techniques. Gut mucosal acidosis was assessed by air tonometry, and ileal wall biopsies were analysed for mitochondrial activity. RESULTS: After 24 h of endotoxaemia, the animals had developed hyperdynamic shock with systemic and mucosal acidosis. Although superior mesenteric artery (SMA) flow was higher than the baseline values, ileal microcirculatory perfusion and mitochondrial complex I activity decreased. After norepinephrine was started, SMA flow, ileal microcirculation, and mucosal acidosis remained unchanged. Although no statistically significant difference could be demonstrated, norepinephrine increased mitochondrial complex I activity in five of the six animals from which ileal biopsies were taken. CONCLUSIONS: Although fluid resuscitated endotoxaemic shock increased regional blood flow, microcirculatory and mitochondrial alterations were still present. Restoring MAP with norepinephrine did not affect ileal microcirculation or mucosal acidosis, indicating that perfusion pressure manipulation is of limited importance to the intestinal microcirculation in established endotoxaemic shock.

Early predictors of morbidity and mortality in trauma patients treated in the intensive care unit.

BACKGROUND: We investigated the incidence and severity of post-injury morbidity and mortality in intensive care unit (ICU)-treated trauma patients. We also identified risk factors in the early phase after injury that predicted the later development of complications. METHODS: A prospective observational cohort study design was used. One hundred and sixty-four adult patients admitted to the ICU for more than 24 h were included during a 21-month period. The incidence and severity of morbidity such as multiple organ failure (MOF), acute lung injury (ALI), severe sepsis and 30-day post-injury mortality were calculated and risk factors were analyzed with uni- and multivariable logistic regression analysis. RESULTS: The median age was 40 years, the injury severity score was 24, the new injury severity score was 29, the acute physiology and chronic health evaluation II score was 15, sequential organ failure assessment maximum was 7 and ICU length of stay was 3.1 days. The incidences of post-injury MOF were 40.2%, ALI 25.6%, severe sepsis 31.1% and 30-day mortality 10.4%. The independent risk factors differed to some extent between the outcome parameters. Age, severity of injury, significant head injury and massive transfusion were independent risk factors for several outcome parameters. Positive blood alcohol was only a predictor of MOF, whereas prolonged rescue time only predicted death. Unexpectedly, injury severity was not an independent risk factor for mortality. CONCLUSIONS: Although the incidence of morbidity was considerable, mortality was relatively low. Early post-injury risk factors that predicted later development of complications differed between morbidity and mortality.

Left ventricular mechanical dyssynchrony is load independent at rest and during endotoxaemia in a porcine model.

AIM: In diseased or injured states, the left ventricle displays higher degrees of mechanical dyssynchrony. We aimed at assessing mechanical dyssynchrony ranges in health related to variation in load as well as during acute endotoxin-induced ventricular injury. METHODS: In 16 juvenile anaesthetized pigs, a five-segment conductance catheter was placed in the left ventricle as well as a balloon-tipped catheter in the inferior vena cava. Mechanical dyssynchrony during systole, including dyssynchrony time in per cent during systole and internal flow fraction during systole, were measured at rest and during controlled pre-load reduction sequences, as well as during 3 h of endotoxin infusion (0.25 microg kg(-)1 h(-1)). RESULTS: Systolic dyssynchrony and internal flow fraction did not change during the course of acute beat-to-beat pre-load alteration. Endotoxin-produced acute pulmonary hypertension by left ventricular dyssynchrony measures was not changed during the early peak of pulmonary hypertension. Endotoxin ventricular injury led to progressive increases in systolic mechanical segmental dyssynchrony (7.9 +/- 1.2-13.0 +/- 1.3%) and ventricular systolic internal flow fraction (7.1 +/- 2.4-16.6 +/- 2.8%), respectively for baseline and then at hour 3. There was no localization of dyssynchrony changes to segment or region in the ventricular long axis during endotoxin infusion. CONCLUSION: These results suggest that systolic mechanical dyssynchrony measures may be load independent in health and during acute global ventricular injury by endotoxin. More study is needed to validate ranges in health and disease for parameters of mechanical dyssynchrony.

Cardiac effects of endothelin receptor antagonism in endotoxemic pigs.

Myocardial depression in sepsis is frequently encountered clinically and contributes to morbidity and mortality. Increased plasma levels of endothelin-1 (ET-1) have been described in septic shock, and previous reports have shown beneficial effects on cardiovascular performance and survival in septic models using ET receptor antagonists. The aim of the current study was to investigate specific cardiac effects of ET receptor antagonism in endotoxicosis. Sixteen domestic pigs were anesthetized and subjected to endotoxin for 5 h. Eight of these pigs were given tezosentan (dual ET receptor antagonist) after 3 h. Cardiac effects were evaluated using the left ventricular (LV) pressure-volume relationship. Endotoxin was not associated with any effects on parameters of LV contractile function [end-systolic elastance (Ees), preload recruitable stroke work (PRSW), power(max)/end-diastolic volume (PWR(max)/EDV) and dP/dt(max)/end-diastolic volume (dP/dt(max)/EDV)] but with impairments in isovolumic relaxation (time constant for pressure decay, tau) and mechanical efficiency. Tezosentan administration decreased Ees, PWR(max)/EDV, and dP/dt(max)/EDV, while improving tau and LV stiffness. Thus, dual ET receptor antagonism was associated with a decline in contractile function but, in contrast, improved diastolic function. Positive hemodynamic effects from ET receptor antagonism in acute endotoxemia may be due to changes in cardiac load and enhanced diastolic function rather than improved contractile function.

Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo.

The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to 1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4 +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (tau from 43.3 +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.

A practice survey on vasopressor and inotropic drug therapy in Scandinavian intensive care units.

BACKGROUND: This practice survey was performed to analyse the indications for use of vasopressor/inotropic drugs, preferred drugs and doses as well as concomitant monitoring and desired haemodynamic target values in Scandinavian ICUs. An internet-based reporting system was implemented. METHODS: A total of 223 ICUs were identified in the Scandinavian countries and invited to participate in a one-day point-prevalence study. An internet-based database was constructed and a practice survey protocol designed to identify haemodynamic monitoring, indications for vasopressor/inotropic drug-therapy, fluids used for volume loading, pretreatment circulatory state, actual and targeted haemodynamic variables. Patients were eligible for the study if on vasopressor/inotropic drug-therapy for more than 4 h. RESULTS: A total of 114 ICUs participated. A total of 114 adult patients matched the inclusion criteria. Sixty-seven per cent of the patients had received vasopressor/inotropic drug-treatment for >24 h and 32% received more than one drug. Arterial hypotension (92%) and oliguria (50%) were most common indications. Fluid loading prior to therapy was reported in 87% of patients. Dopamine (47%) and noradrenaline (44%) were the most commonly used drugs followed by dobutamine (24%). No other drug exceeded 6%. Non-catecholamine drugs were rarely used even in cardiac failure patients. Invasive arterial pressure was monitored in 95% of patients, pulmonary artery catheters were used in 19%. Other cardiac output monitoring techniques were used in 8.5% of the patients. CONCLUSION: Dopamine and noradrenaline seem to be the most commonly used inotropic/vasopressor drugs in Scandinavia. Traditional indications for inotropic/vasopressor support as hypotension and oliguria seem to be most common. Invasive monitoring was used in almost all patients, whereas a limited use of pulmonary artery catheters was noted. The internet-based reporting system proved to be an efficient tool for data collection.

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.

Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock.

BACKGROUND: Cardiac dysfunction during septic shock is well described but the underlying mechanisms still remain to be resolved. This study was conducted to elucidate the involvement of endothelin in cardiac function during endotoxin shock by the use of endothelin receptor antagonism. METHODS: Anaesthetised and haemodynamically stable landrace pigs received the nonpeptide mixed endothelin receptor antagonist bosentan, two hours after onset of endotoxaemia (n=7). Cardiopulmonary vascular changes, including cardiac index, stroke work index, coronary artery blood flow, rate of change of left ventricular pressure (dp/dt), and arterial and coronary sinus plasma levels of endothelin-1-like immunoreactivity were compared to a control group only receiving endotoxin (n=7). RESULTS: Plasma endothelin-1-like immunoreactivity increased threefold in the control group. Bosentan effectively counteracted the endotoxin induced decrease in cardiac index. This was accompanied by a significant reduction of both right and left ventricular afterload. In addition, coronary artery blood flow increased and coronary vascular resistance decreased compared to controls. Dp/dt remained unaffected by endothelin receptor antagonism. A further increase in plasma endothelin-1-like immunoreactivity was seen in response to bosentan. CONCLUSION: These results indicate that the increased endothelin production during endotoxaemia contributes to a depressed cardiac performance and that endothelin receptor antagonism may counteract this development. Possible mechanisms for the improved cardiac performance include both a reduction of afterload and enhanced coronary blood flow.