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1.  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.
doi:10.1186/1752-1947-8-28
PMCID: PMC3917414  PMID: 24467750
Acute heart failure; Angioedema; C1 inhibitor deficiency; Dermatomyositis; Shock; Systemic capillary leak
2.  National intensive care unit bed capacity and ICU patient characteristics in a low income country 
BMC Research Notes  2012;5:475.
Background
Primary health care delivery in the developing world faces many challenges. Priority setting favours HIV, TB and malaria interventions. Little is known about the challenges faced in this setting with regard to critical care medicine. The aim of this study was to analyse and categorise the diagnosis and outcomes of 1,774 patients admitted to a hospital intensive care unit (ICU) in a low-income country over a 7-year period. We also assessed the country’s ICU bed capacity and described the challenges faced in dealing with critically ill patients in this setting.
Findings
A retrospective audit was conducted in a general ICU in a university hospital in Uganda. Demographic data, admission diagnosis, and ICU length of stay were recorded for the 1,774 patients who presented to the ICU in the period January 2003 to December 2009. Their mean age was 35.5 years. Males accounted for 56.5% of the study population; 92.8% were indigenous, and 42.9% were referrals from upcountry units. The average mortality rate over the study period was 40.1% (n = 715). The highest mortality rate (44%) was recorded in 2004 and the lowest (33.2%) in 2005. Children accounted for 11.6% of admissions (40.1% mortality). Sepsis, ARDS, traumatic brain injuries and HIV related conditions were the most frequent admission diagnoses. A telephonic survey determined that there are 33 adult ICU beds in the whole country.
Conclusions
Mortality was 40.1%, with sepsis, head injury, acute lung injury and HIV/AIDS the most common admission diagnoses. The country has a very low ICU bed capacity. Prioritising infectious diseases poses a challenge to ensuring that critical care is an essential part of the health care package in Uganda.
doi:10.1186/1756-0500-5-475
PMCID: PMC3470976  PMID: 22937769
Intensive care medicine; Diagnosis; Uganda; Low-income country; Mortality
4.  Recommendations for sepsis management in resource-limited settings 
Intensive Care Medicine  2012;38(4):557-574.
Purpose
To provide clinicians practicing in resource-limited settings with a framework to improve the diagnosis and treatment of pediatric and adult patients with sepsis.
Methods
The medical literature on sepsis management was reviewed. Specific attention was paid to identify clinical evidence on sepsis management from resource-limited settings.
Results
Recommendations are grouped into acute and post-acute interventions. Acute interventions include liberal fluid resuscitation to achieve adequate tissue perfusion, normal heart rate and arterial blood pressure, use of epinephrine or dopamine for inadequate tissue perfusion despite fluid resuscitation, frequent measurement of arterial blood pressure in hemodynamically unstable patients, administration of hydrocortisone or prednisolone to patients requiring catecholamines, oxygen administration to achieve an oxygen saturation >90%, semi-recumbent and/or lateral position, non-invasive ventilation for increased work of breathing or hypoxemia despite oxygen therapy, timely administration of adequate antimicrobials, thorough clinical investigation for infectious source identification, fluid/tissue sampling and microbiological work-up, removal, drainage or debridement of the infectious source. Post-acute interventions include regular re-assessment of antimicrobial therapy, administration of antimicrobials for an adequate but not prolonged duration, avoidance of hypoglycemia, pharmacological or mechanical deep vein thrombosis prophylaxis, resumption of oral food intake after resuscitation and regaining of consciousness, careful use of opioids and sedatives, early mobilization, and active weaning of invasive support. Specific considerations for malaria, puerperal sepsis and HIV/AIDS patients with sepsis are included.
Conclusion
Only scarce evidence exists for the management of pediatric and adult sepsis in resource-limited settings. The presented recommendations may help to improve sepsis management in middle- and low-income countries.
Electronic supplementary material
The online version of this article (doi:10.1007/s00134-012-2468-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s00134-012-2468-5
PMCID: PMC3307996  PMID: 22349419
Sepsis; Intensive care; Resource-limited settings; Middle-income countries; Low-income countries; Recommendations; Management
5.  Facing medical care problems of victims of sexual violence in Goma/Eastern Democratic Republic of the Congo 
Background
Since 1998, the Eastern Democratic Republic of the Congo has been torn by a military conflict. A particular atrocity of the war is widespread sexual violence.
Methods
In this combined retrospective analysis and prospective survey, we sought to identify hospital facilities and resources available to treat victims of sexual violence in Goma, the capital city of the North Kivu province.
Results
Of twenty-three acute care hospitals registered in the area of Goma, four (17%) regularly cared for victims of sexual violence. One hospital had all resources always available to appropriately care for victims of sexual violence. From Jan 2009 until Oct 2010, 7,048 females sought medical care because of physical or psychological sequelae from sexual violence in the four hospitals of Goma. Only half of the hospitals had physicians specialized in gynaecology or gynaecological surgery available. Similarly, anaesthetists and psychiatrists/psychologists were available in two (50%) and one (25%) hospital, respectively. Post-discharge care facilities, material resources, such as surgical and anaesthesiological equipment and drugs, were inconsistently available in the hospitals caring for sexually abused females. At one selected hospital, acyclovir and/or antibiotics were administered to 1,202 sexually abused females (89.5%), whereas post-exposure HIV prophylaxis and surgery because of vesico-vaginal fistula was provided to only 75 (5.6%) and 121 (9%) patients, respectively.
Conclusions
This study provides data that only few hospitals in Goma care for victims of sexual violence. In addition, these hospitals suffer from a relevant shortage of human and material resources to provide adequate care for sexually abused females. Aside from establishment of adequate protection strategies, steps must be taken to increase the availability of trained health care professionals and resources to provide adequate care for victims of sexual violence in Goma and the North Kivu province.
doi:10.1186/1752-1505-5-2
PMCID: PMC3059296  PMID: 21375778
6.  Availability of critical care resources to treat patients with severe sepsis or septic shock in Africa: a self-reported, continent-wide survey of anaesthesia providers 
Critical Care  2011;15(1):R10.
Introduction
It is unknown whether resources necessary to implement the Surviving Sepsis Campaign guidelines and sepsis bundles are available in Africa. This self-reported, continent-wide survey compared the availability of these resources between African and high-income countries, and between two African regions (Sub-Sahara Africa vs. South Africa, Mauritius and the Northern African countries).
Methods
The study was conducted as an anonymous questionnaire-based, cross-sectional survey among anaesthesia providers attending a transcontinental congress. Based on the respondents' country of practice, returned questionnaires were grouped into African and high-income countries. The questionnaire contained 74 items and evaluated all material resources required to implement the most recent Surviving Sepsis Campaign guidelines. Group comparisons were performed with the Chi2, Fisher's Exact or Mann Whitney U test, as appropriate.
Results
The overall response rate was 74.3% (318/428). Three-hundred-seven questionnaires were analysed (African countries, n = 263; high-income countries, n = 44). Respondents from African hospitals were less likely to have an emergency room (85.5 vs. 97.7%, P = 0.03) or intensive care unit (73.8 vs. 100%, P < 0.001) than respondents from high-income countries. Drugs, equipment, and disposable materials required to implement the Surviving Sepsis Campaign guidelines or sepsis bundles were less frequently available in African than high-income countries. Of all African and Sub-Saharan African countries, 1.5% (4/263) and 1.2% (3/248) of respondents had the resources available to implement the Surviving Sepsis Campaign guidelines in entirety. The percentage of implementable recommendations was lower in African than in high-income countries (72.6 (57.7 to 87.7)% vs. 100 (100 to 100)%, P < 0.001) and lower in Sub-Saharan African countries than South Africa, Mauritius, and the Northern African countries (72.6 (56.2 to 86.3)% vs. 90.4 (71.2 to 94.5)%, P = 0.02).
Conclusions
The results of this self-reported survey strongly suggest that the most recent Surviving Sepsis guidelines cannot be implemented in Africa, particularly not in Sub-Saharan Africa, due to a shortage of required hospital facilities, equipment, drugs and disposable materials. However, availability of resources to implement the majority of strong Surviving Sepsis Campaign recommendations and the sepsis bundles may allow modification of current sepsis guidelines based on available resources and implementation of a substantial number of life-saving interventions into sepsis care in Africa.
doi:10.1186/cc9410
PMCID: PMC3222039  PMID: 21219619
7.  Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study 
Critical Care  2010;14(6):R200.
Introduction
V2-receptor (V2R) stimulation potentially aggravates sepsis-induced vasodilation, fluid accumulation and microvascular thrombosis. Therefore, the present study was performed to determine the effects of a first-line therapy with the selective V2R-antagonist (Propionyl1-D-Tyr(Et)2-Val4-Abu6-Arg8,9)-Vasopressin on cardiopulmonary hemodynamics and organ function vs. the mixed V1aR/V2R-agonist arginine vasopressin (AVP) or placebo in an established ovine model of septic shock.
Methods
After the onset of septic shock, chronically instrumented sheep were randomly assigned to receive first-line treatment with the selective V2R-antagonist (1 μg/kg per hour), AVP (0.05 μg/kg per hour), or normal saline (placebo, each n = 7). In all groups, open-label norepinephrine was additionally titrated up to 1 μg/kg per minute to maintain mean arterial pressure at 70 ± 5 mmHg, if necessary.
Results
Compared to AVP- and placebo-treated animals, the selective V2R-antagonist stabilized cardiopulmonary hemodynamics (mean arterial and pulmonary artery pressure, cardiac index) as effectively and increased intravascular volume as suggested by higher cardiac filling pressures. Furthermore, left ventricular stroke work index was higher in the V2R-antagonist group than in the AVP group. Notably, metabolic (pH, base excess, lactate concentrations), liver (transaminases, bilirubin) and renal (creatinine and blood urea nitrogen plasma levels, urinary output, creatinine clearance) dysfunctions were attenuated by the V2R-antagonist when compared with AVP and placebo. The onset of septic shock was associated with an increase in AVP plasma levels as compared to baseline in all groups. Whereas AVP plasma levels remained constant in the placebo group, infusion of AVP increased AVP plasma levels up to 149 ± 21 pg/mL. Notably, treatment with the selective V2R-antagonist led to a significant decrease of AVP plasma levels as compared to shock time (P < 0.001) and to both other groups (P < 0.05 vs. placebo; P < 0.001 vs. AVP). Immunohistochemical analyses of lung tissue revealed higher hemeoxygenase-1 (vs. placebo) and lower 3-nitrotyrosine concentrations (vs. AVP) in the V2R-antagonist group. In addition, the selective V2R-antagonist slightly prolonged survival (14 ± 1 hour) when compared to AVP (11 ± 1 hour, P = 0.007) and placebo (11 ± 1 hour, P = 0.025).
Conclusions
Selective V2R-antagonism may represent an innovative therapeutic approach to attenuate multiple organ dysfunction in early septic shock.
doi:10.1186/cc9320
PMCID: PMC3220000  PMID: 21054850
8.  Brain herniation in a patient with apparently normal intracranial pressure: a case report 
Introduction
Intracranial pressure monitoring is commonly implemented in patients with neurologic injury and at high risk of developing intracranial hypertension, to detect changes in intracranial pressure in a timely manner. This enables early and potentially life-saving treatment of intracranial hypertension.
Case presentation
An intraparenchymal pressure probe was placed in the hemisphere contralateral to a large basal ganglia hemorrhage in a 75-year-old Caucasian man who was mechanically ventilated and sedated because of depressed consciousness. Intracranial pressures were continuously recorded and never exceeded 17 mmHg. After sedation had been stopped, our patient showed clinical signs of transtentorial brain herniation, despite apparently normal intracranial pressures (less than 10 mmHg). Computed tomography revealed that the size of the intracerebral hematoma had increased together with significant unilateral brain edema and transtentorial herniation. The contralateral hemisphere where the intraparenchymal pressure probe was placed appeared normal. Our patient underwent emergency decompressive craniotomy and was tracheotomized early, but did not completely recover.
Conclusions
Intraparenchymal pressure probes placed in the hemisphere contralateral to an intracerebral hematoma may dramatically underestimate intracranial pressure despite apparently normal values, even in the case of transtentorial brain herniation.
doi:10.1186/1752-1947-4-297
PMCID: PMC2936928  PMID: 20807427
9.  Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial 
Critical Care  2009;13(6):R181.
Introduction
It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock.
Methods
This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP ≥ 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles ≥ 70 mmHg and mortality or the frequency and occurrence of disease-related events.
Results
There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01).
Conclusions
MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.
doi:10.1186/cc8167
PMCID: PMC2811945  PMID: 19917106
10.  Hemodynamic variables and mortality in cardiogenic shock: a retrospective cohort study 
Critical Care  2009;13(5):R157.
Introduction
Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality.
Methods
Medical records and the patient data management system of a multidisciplinary intensive care unit (ICU) were reviewed for patients admitted because of cardiogenic shock. In all patients, the hourly variable time integral of hemodynamic variables during the first 24 hours after ICU admission was calculated. If hemodynamic variables were associated with 28-day mortality, the hourly variable time integral of drops below clinically relevant threshold levels was computed. Regression models and receiver operator characteristic analyses were calculated. All statistical models were adjusted for age, admission year, mean catecholamine doses and the Simplified Acute Physiology Score II (excluding hemodynamic counts) in order to account for the influence of age, changes in therapies during the observation period, the severity of cardiovascular failure and the severity of the underlying disease on 28-day mortality.
Results
One-hundred and nineteen patients were included. Cardiac index (CI) (P = 0.01) and cardiac power index (CPI) (P = 0.03) were the only hemodynamic variables separately associated with mortality. The hourly time integral of CI drops <3, 2.75 (both P = 0.02) and 2.5 (P = 0.03) L/min/m2 was associated with death but not that of CI drops <2 L/min/m2 or lower thresholds (all P > 0.05). The hourly time integral of CPI drops <0.5-0.8 W/m2 (all P = 0.04) was associated with 28-day mortality but not that of CPI drops <0.4 W/m2 or lower thresholds (all P > 0.05).
Conclusions
During the first 24 hours after intensive care unit admission, CI and CPI are the most important hemodynamic variables separately associated with 28-day mortality in patients with cardiogenic shock. A CI of 3 L/min/m2 and a CPI of 0.8 W/m2 were most predictive of 28-day mortality. Since our results must be considered hypothesis-generating, randomized controlled trials are required to evaluate whether targeting these levels as early resuscitation endpoints can improve mortality in cardiogenic shock.
doi:10.1186/cc8114
PMCID: PMC2784383  PMID: 19799772
11.  Report from Mongolia – How much do we know about the incidence of rare cases in less developed countries: a case series 
Introduction
Case reports are important instruments to describe rare disease conditions and give a rough estimation of their global incidence. Even though collected in international databases, most case reports are published by clinicians from industrialized nations and little is known about the incidence of rare cases in less developed countries, which are home to 75% of the world's population.
Case presentation
We present seven patients who suffered from diseases which are either considered to be rare or have not yet been described before according to international databases, but occurred during a 5-month period in one intensive care unit of a less developed country. During the observation period, patients with a spontaneous infratentorial subdural hematoma (Asian, female, 41 years), general exanthema and acute renal failure after diesel ingestion (Asian, male, 30 years), transient cortical blindness complicating hepatic encephalopathy (Asian, female, 49 years), Fournier gangrene complicating acute necrotizing pancreatitis (Asian, male, 37 years), acute renal failure due to acetic acid intoxication (Asian, male, 42 years), haemolytic uremic syndrome following septic abortion (Asian, female, 45 years), and a metal needle as an unusual cause of chest pain (Asian, male, 41 years) were treated. According to the current literature, all seven disease conditions are considered either rare or have so far not yet been reported.
Conclusion
The global incidence of rare cases may be underestimated by contemporary international databases. Diseases which are currently considered to be rare in industrialized nations may occur at a higher frequency in less developed countries. Reasons may not only be a geographically different burden of certain diseases, limited diagnostic and therapeutic facilities, but also a relevant publication bias.
doi:10.1186/1752-1947-2-358
PMCID: PMC2605759  PMID: 19032758
12.  Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression 
Critical Care  2008;12(4):R99.
Introduction
The multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function.
Methods
This retrospective analysis summarizes our preliminary clinical experience with the combined use of milrinone and enteral metoprolol therapy in 40 patients with septic shock and cardiac depression. Patients with other causes of shock or cardiac failure, patients with beta-blocker therapy initiated more than 48 hours after shock onset, and patients with pre-existent decompensated congestive heart failure were excluded. In all study patients, beta blockers were initiated only after stabilization of cardiovascular function (17.7 ± 15.5 hours after shock onset or intensive care unit admission) in order to decrease the heart rate to less than 95 beats per minute (bpm). Hemodynamic data and laboratory parameters were extracted from medical charts and documented before and 6, 12, 24, 48, 72, and 96 hours after the first metoprolol dosage. Adverse cardiovascular events were documented. Descriptive statistical methods and a linear mixed-effects model were used for statistical analysis.
Results
Heart rate control (65 to 95 bpm) was achieved in 97.5% of patients (n = 39) within 12.2 ± 12.4 hours. Heart rate, central venous pressure, and norepinephrine, arginine vasopressin, and milrinone dosages decreased (all P < 0.001). Cardiac index and cardiac power index remained unchanged whereas stroke volume index increased (P = 0.002). In two patients (5%), metoprolol was discontinued because of asymptomatic bradycardia. Norepinephrine and milrinone dosages were increased in nine (22.5%) and six (15%) patients, respectively. pH increased (P < 0.001) whereas arterial lactate (P < 0.001), serum C-reactive protein (P = 0.001), and creatinine (P = 0.02) levels decreased during the observation period. Twenty-eight-day mortality was 33%.
Conclusion
Low doses of enteral metoprolol in combination with phosphodiesterase inhibitors are feasible in patients with septic shock and cardiac depression but no overt heart failure. Future prospective controlled trials on the use of beta blockers for septic cardiomyopathy and their influence on proinflammatory cytokines are warranted.
doi:10.1186/cc6976
PMCID: PMC2575588  PMID: 18680591
13.  Vasopressor stays vasopressor and inotrope stays inotrope! 
Critical Care  2008;12(2):415.
doi:10.1186/cc6850
PMCID: PMC2447587  PMID: 18423070
14.  Vasopressin in vasodilatory shock: ensure organ blood flow, but take care of the heart! 
Critical Care  2006;10(6):172.
Supplementary arginine vasopressin infusion in advanced vasodilatory shock may be accompanied by a decrease in cardiac index and systemic oxygen transport capacity in approximately 40% of patients. While a reduction of cardiac output most frequently occurs in patients with hyperdynamic circulation, it is less often observed in patients with low cardiac index. Infusion of inotropes, such as dobutamine, may be an effective strategy to restore systemic blood flow. However, when administering inotropic drugs, systemic blood flow should be increased to adequately meet systemic demands (assessed by central or mixed venous oxygen saturation) without putting an excessive beta-adrenergic stress on the heart. Overcorrection of cardiac index to hyperdynamic values with inotropes places myocardial oxygen supply at significant risk.
doi:10.1186/cc5089
PMCID: PMC1794457  PMID: 17129364
15.  Causes of death and determinants of outcome in critically ill patients 
Critical Care  2006;10(6):R154.
Introduction
Whereas most studies focus on laboratory and clinical research, little is known about the causes of death and risk factors for death in critically ill patients.
Methods
Three thousand seven hundred patients admitted to an adult intensive care unit (ICU) were prospectively evaluated. Study endpoints were to evaluate causes of death and risk factors for death in the ICU, in the hospital after discharge from ICU, and within one year after ICU admission. Causes of death in the ICU were defined according to standard ICU practice, whereas deaths in the hospital and at one year were defined and grouped according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) score. Stepwise logistic regression analyses were separately calculated to identify independent risk factors for death during the given time periods.
Results
Acute, refractory multiple organ dysfunction syndrome was the most frequent cause of death in the ICU (47%), and central nervous system failure (relative risk [RR] 16.07, 95% confidence interval [CI] 8.3 to 31.4, p < 0.001) and cardiovascular failure (RR 11.83, 95% CI 5.2 to 27.1, p < 0.001) were the two most important risk factors for death in the ICU. Malignant tumour disease and exacerbation of chronic cardiovascular disease were the most frequent causes of death in the hospital (31.3% and 19.4%, respectively) and at one year (33.2% and 16.1%, respectively).
Conclusion
In this primarily surgical critically ill patient population, acute or chronic multiple organ dysfunction syndrome prevailed over single-organ failure or unexpected cardiac arrest as a cause of death in the ICU. Malignant tumour disease and chronic cardiovascular disease were the most important causes of death after ICU discharge.
doi:10.1186/cc5086
PMCID: PMC1794454  PMID: 17083735
16.  Arteriolar vasoconstrictive response: comparing the effects of arginine vasopressin and norepinephrine 
Critical Care  2006;10(3):R75.
Introduction
This study was designed to examine differences in the arteriolar vasoconstrictive response between arginine vasopressin (AVP) and norepinephrine (NE) on the microcirculatory level in the hamster window chamber model in unanesthetized, normotonic hamsters using intravital microscopy. It is known from patients with advanced vasodilatory shock that AVP exerts strong additional vasoconstriction when incremental dosage increases of NE have no further effect on mean arterial blood pressure (MAP).
Methods
In a prospective controlled experimental study, eleven awake, male golden Syrian hamsters were instrumented with a viewing window inserted into the dorsal skinfold. NE (2 μg/kg/minute) and AVP (0.0001 IU/kg/minute, equivalent to 4 IU/h in a 70 kg patient) were continuously infused to achieve a similar increase in MAP. According to their position within the arteriolar network, arterioles were grouped into five types: A0 (branch off small artery) to A4 (branch off A3 arteriole).
Results
Reduction of arteriolar diameter (NE, -31 ± 12% versus AVP, -49 ± 7%; p = 0.002), cross sectional area (NE, -49 ± 17% versus AVP, -73 ± 7%; p = 0.002), and arteriolar blood flow (NE, -62 ± 13% versus AVP, -80 ± 6%; p = 0.004) in A0 arterioles was significantly more pronounced in AVP animals. There was no difference in red blood cell velocities in A0 arterioles between groups. The reduction of diameter, cross sectional area, red blood cell velocity, and arteriolar blood flow in A1 to A4 arterioles was comparable in AVP and NE animals.
Conclusion
Within the microvascular network, AVP exerted significantly stronger vasoconstriction on large A0 arterioles than NE under physiological conditions. This observation may partly explain why AVP is such a potent vasopressor hormone and can increase systemic vascular resistance even in advanced vasodilatory shock unresponsive to increases in standard catecholamine therapy.
doi:10.1186/cc4922
PMCID: PMC1550934  PMID: 16696866
17.  Cutaneous vascular reactivity and flow motion response to vasopressin in advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome 
Critical Care  2006;10(2):R40.
Introduction
Disturbances in microcirculatory homeostasis have been hypothesized to play a key role in the pathophysiology of multiple organ dysfunction syndrome and vasopressor-associated ischemic skin lesions. The effects of a supplementary arginine vasopressin (AVP) infusion on microcirculation in vasodilatory shock and postoperative multiple organ dysfunction syndrome are unknown.
Method
Included in the study were 18 patients who had undergone cardiac or major surgery and had a mean arterial blood pressure below 65 mmHg, despite infusion of more than 0.5 μg/kg per min norepinephrine. Patients were randomly assigned to receive a combined infusion of AVP/norepinephrine or norepinephrine alone. Demographic and clinical data were recorded at study entry and after 1 hour. A laser Doppler flowmeter was used to measure the cutaneous microcirculatory response at randomization and after 1 hour. Reactive hyperaemia and oscillatory changes in the Doppler signal were measured during the 3 minutes before and after a 5-minute period of forearm ischaemia.
Results
Patients receiving AVP/norepinephrine had a significantly higher mean arterial pressure (P = 0.047) and higher milrinone requirements (P = 0.025) than did the patients who received norepinephrine only at baseline. Mean arterial blood pressure significantly increased (P < 0.001) and norepinephrine requirements significantly decreased (P < 0.001) in the AVP/norepinephrine group. Patients in the AVP/norepinephrine group exhibited a significantly higher oscillation frequency of the Doppler signal before ischaemia and during reperfusion at randomization. During the study period, there were no differences in either cutaneous reactive hyperaemia or the oscillatory pattern of vascular tone between groups.
Conclusion
Supplementary AVP infusion in patients with advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome did not compromise cutaneous reactive hyperaemia and flowmotion when compared with norepinephrine infusion alone.
doi:10.1186/cc4845
PMCID: PMC1550871  PMID: 16542484
18.  Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study 
Critical Care  2005;9(5):R541-R548.
Introduction
Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients.
Methods
AFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin.
Results
Four hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels <0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels.
Conclusion
Standard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis.
doi:10.1186/cc3792
PMCID: PMC1297619  PMID: 16277716

Results 1-18 (18)