A young male with epitheliolysis in the small bowel and colon.

Background: Toxic epidermal necrolysis (TEN) is characterized by epidermal necrosis of various degree, and can affect the entire body surface. Affection of small bowel and colon is a rare manifestation of TEN. We present a case with an unusual appearance of epitheliolysis of the small bowel and colon due to a toxic reaction.Case report: A 19 year old male was diagnosed with ulcerative colitis (UC) after treatment with tetracyclines followed by isotretinoin due to acne vulgaris. Medical treatment did not lead to improvement of his UC, and an emergency resection of the colon was performed. Postoperatively his condition worsened due to small bowel epitheliolysis, and he recovered finally 6 months later after a partial small bowel resection.Conclusion: The true cause of this very serious situation with severe gastrointestinal involvement is not fully understood. In this case, successive treatment with antibiotics and isotretinoin given to a patient with an inflamed colon might have triggered the destruction of the epithelial barrier, leading to an immense immunological reaction in the intestinal wall. We suggest that physicians should be aware of UC-like symptoms occurring prior to or during treatment with tetracyclines and/or isotretinoin.

Microcirculation and red cell transfusion in patients with sepsis.

Early identification of sepsis followed by diagnostic blood cultures and prompt administration of appropriate intravenous antibiotics covering all likely pathogen remains the corner stone in the initial management of sepsis. Source control, obtained by harvesting microbiological cultures and removal or drainage of the infected foci, is mandatory. However, optimization of hemodynamically unstable patients including volume support supplemented with vasopressor, inotropic and transfusion of red blood cells (RBCs) in case of persistent hypoperfusion have the potential to reduce morbidity and mortality. Given the imbalance between the ability of the cardiovascular system to deliver enough oxygen to meet the oxygen demand, transfusion of RBCs should theoretically provide the ideal solution to the challenge. However, both changes in the septic patients' RBCs induced by endogenous factors as well as the storage lesion affecting transfused RBCs have negative effects on the microcirculation. RBC morphology, distribution of fatty acids on the membrane surface, RBC deformability needed for capillary circulation and the nitrogen oxide (NO) signaling systems are involved. Although these deteriorating effects develop during storage, transfusion of fresh RBCs has not proven to be beneficial, possibly due to limitations of the studies performed. Until better evidence exists, transfusion guidelines recommend a restrictive strategy of RBC transfusion i.e. transfuse when hemoglobin (Hb)<7g/dL in septic patients.

Acute elevation of intra-abdominal pressure contributes to extravascular shift of fluid and proteins in an experimental porcine model.

BACKGROUND: Intra-abdominal hypertension and abdominal compartment syndrome contribute significantly to increased morbidity and mortality in critically ill patients. This study describes pathophysiologic effects of the acutely elevated intra-abdominal pressure on microvascular fluid exchange and microcirculation. The resulting changes could contribute to development of organ dysfunction or failure. METHODS: 16 pigs were randomly allocated to a control-group (C-group) or an interventional group (P-group). After 60 min of stabilization, intra-abdominal pressure of the P-group animals was elevated to 15 mmHg by Helium insufflation and after 120 min to a level of 30 mmHg for two more hours. The C-group animals were observed without insufflation of gas. Laboratory and hemodynamic parameters, plasma volume, plasma colloid osmotic pressure, total tissue water content, tissue perfusion, markers of inflammation and cerebral energy metabolism were measured and net fluid balance and fluid extravasation rates calculated. Analysis of variance for repeated measurements with post-tests were used to evaluate the results with respect to differences within or between the groups. RESULTS: In the C-group hematocrit, net fluid balance, plasma volume and the fluid extravasation rate remained essentially unchanged throughout the study as opposed to the increase in hematocrit (P < 0.001), fluid extravasation rate (P < 0.05) and decrease in plasma volume (P < 0.001) of the P-group. Hemodynamic parameters remained stable or were slightly elevated in the C-group while the P-group demonstrated an increase in femoral venous pressure (P < 0.001), right atrial pressure (P < 0.001), pulmonary capillary wedge pressure (P < 0.01) and mean pulmonary arterial pressure (P < 0.001). The protein mass decreased in both study groups but was significantly lower in the P-group as compared with the C-group, after 240 min of intervention. The increased intra-abdominal pressure was associated with elevated intracranial pressure and reduced tissue perfusion of the pancreas and the gastric- and intestinal mucosa. CONCLUSION: Elevation of intra-abdominal pressure has an immediate impact on microvascular fluid extravasation leading to plasma volume contraction, reduced cardiac output and deranged perfusion of abdominal organs.

Aetiology, antimicrobial therapy and outcome of patients with community acquired severe sepsis: a prospective study in a Norwegian university hospital.

BACKGROUND: Severe sepsis is recognized as an inflammatory response causing organ dysfunction in patients with infection. Antimicrobial therapy is the mainstay of treatment. There is an ongoing demand for local surveillance of sepsis aetiology and monitoring of empirical treatment recommendations. The present study was established to describe the characteristics, quality of handling and outcome of patients with severe sepsis admitted to a Norwegian university hospital. METHODS: A one year prospective, observational study of adult community acquired case-defined severe sepsis was undertaken. Demographics, focus of infection, microbiological findings, timing and adequacy of empirical antimicrobial agents were recorded. Clinical diagnostic practice was evaluated. Differences between categorical groups were analysed with Pearson's chi-squared test. Predictors of in-hospital mortality were identified in a multivariate stepwise backward logistic regression model. RESULTS: In total 220 patients were identified, yielding an estimated annual incidence of 0.5/1000 inhabitants. The focus of infection was established at admission in 69%. Respiratory tract infection was present in 52%, while genitourinary, soft tissue and abdominal infections each were found in 12-14%. Microbiological aetiology was identified in 61%; most prevalent were Streptococcus pneumoniae, Escherichia coli and Staphylococcus aureus. Independent predictors of in-hospital mortality were malignancy, cardiovascular disease, endocarditis, abdominal infections, undefined microbiological aetiology, delay in administration of empirical antimicrobial agents ≥ 6 hours and use of inadequate antimicrobial agents. In patients ≥ 75 years, antimicrobial therapy was less in compliance with current recommendations and more delayed. CONCLUSIONS: Community acquired severe sepsis is common. Initial clinical aetiology is often revised. Compliance with recommendations for empirical antimicrobial treatment is lowest in elderly patients. Our results emphasizes that quick identification of correct source of infection, proper sampling for microbiological analyses, and fast administration of adequate antimicrobial agents are crucial points in the management of severe sepsis.

Isoflurane in contrast to propofol promotes fluid extravasation during cardiopulmonary bypass in pigs.

BACKGROUND: A highly positive intraoperative fluid balance should be prevented as it negatively impacts patient outcome. Analysis of volume-kinetics has identified an increase in interstitial fluid volume after crystalloid fluid loading during isoflurane anesthesia. Isoflurane has also been associated with postoperative hypoxemia and may be associated with an increase in alveolar epithelial permeability, edema formation, and hindered oxygen exchange. In this article, the authors compare fluid extravasation rates before and during cardiopulmonary bypass (CPB) with isoflurane- versus propofol-based anesthesia. METHODS: Fourteen pigs underwent 2 h of tepid CPB with propofol (P-group; n = 7) or isoflurane anesthesia (I-group; n = 7). Fluid requirements, plasma volume, colloid osmotic pressures in plasma and interstitial fluid, hematocrit levels, and total tissue water content were recorded, and fluid extravasation rates calculated. RESULTS: Fluid extravasation rates increased in the I-group from the pre-CPB level of 0.27 (0.13) to 0.92 (0.36) ml·kg·min, but remained essentially unchanged in the P-group with significant between-group differences during CPB (pb = 0.002). The results are supported by corresponding changes in interstitial colloid osmotic pressure and total tissue water content. CONCLUSIONS: During CPB, isoflurane, in contrast to propofol, significantly contributes to a general increase in fluid shifts from the intravascular to the interstitial space with edema formation and a possible negative impact on postoperative organ function.

Surface cooling versus core cooling: comparative studies of microvascular fluid- and protein-shifts in a porcine model.

OBJECTIVE: To describe how surface cooling compared with core cooling influences fluid and protein distribution, vascular capacity and hemodynamic variables. METHODS: 14 anesthetized piglets were, following 60 min normothermic stabilization, randomly cooled by surface cooling (ice-sludge) (n=7) or core cooling (endovascular cooling) (n=7) to about 28 degrees C. Fluid balance, hemodynamic variables, colloid osmotic pressures (plasma/interstitial fluid), hematocrit, serum-albumin and -protein concentrations, intracranial pressure (ICP) and cerebral metabolic markers of ischemia were measured. Fluid shifts and changes in albumin and protein masses were calculated. At the end total tissue water content was assessed and compared with a normothermic control group. RESULTS: Both cooling modes induced an increase in fluid extravasation rate from 33.9 (31.9) and 27.8 (28.0) to 109.0 (16.5) (P=0.006) and 95.6 (29.1) ml/kg/min x 10(-3) (P=0.024) in the surface-cooled and core-cooled groups, respectively. Albumin extravasation was reflected by a significant drop in the albumin mass from 148.8 (11.7) to 111.4 (10.3) (P=0.000) and from 163.4 (27.8) to 136.8 (19.0) g/kg x 10(-2) (P=0.001) in the surface-cooled and core-cooled animals, respectively. Similar findings were obtained concerning serum-protein masses. The total tissue water content increased in most organs including brain in both study groups compared with a control. ICP and cerebral metabolic markers remained normal in both groups. CONCLUSION: Rapid lowering of body core temperature results in extravasation of water and proteins. The amount of extravated fluid and proteins is similar either cooling is a result of surface cooling or core cooling. Cold-induced fluid extravasation is associated with edema in most tissues including brain.

Fluid overload during cardiopulmonary bypass is effectively reduced by a continuous infusion of hypertonic saline/dextran (HSD).

OBJECTIVE: Cardiopulmonary bypass (CPB) is associated with fluid overload. We examined how a continuous infusion of hypertonic saline/dextran (HSD) influenced fluid shifts during CPB. MATERIALS AND METHODS: Fourteen animals were randomized to a control-group (CT-group) or a hypertonic saline/dextran-group (HSD-group). Ringer's solution was used as CPB-prime and as maintenance fluid at a rate of 5 ml/kg/h. In the HSD group, 1 ml/kg/h of the maintenance fluid was substituted with HSD. After 60 min of normothermic CPB, hypothermic CPB was initiated and continued for 90 min. Fluid was added to the CPB-circuit as needed to maintain a constant level in the venous reservoir. Fluid balance, plasma volume, total tissue water (TTW), intracranial pressure (ICP) and fluid extravasation rates (FER) were measured/calculated. RESULTS: In the HSD-group the fluid need was reduced with 60% during CPB compared with the CT-group. FER was 0.38(0.06) ml/kg/min in the HSD-group and 0.74 (0.16) ml/kg/min in the CT-group. TTW was significantly lower in the heart and some of the visceral organs in the HSD-group. In this group ICP remained stable during CPB, whereas an increase was observed in the CT-group (p<0.01). CONCLUSIONS: A continuous infusion of HSD reduced the fluid extravasation rate and total fluid gain during CPB. TTW was reduced in the heart and some visceral organs. During CPB ICP remained normal in the HSD-group, whereas an increase was present in the CT-group. No adverse effects were observed.

Low perfusion pressure during CPB may induce cerebral metabolic and ultrastructural changes.

BACKGROUND: Recently we reported on cerebral metabolic changes suggesting ischemia in piglets during nitroprusside-induced low-pressure CPB. We here investigated whether a mean arterial pressure (MAP) of 40-45 mmHg could provoke similar changes by a NO-independent intervention. METHODS: Piglets underwent 60 minutes normothermic followed by 90 minutes hypothermic CPB. The LP-group (n=8) had MAP of 40-45 mmHg by phentolamine while the HP-group (n=8) had MAP of 60-80 mmHg by norepinephrine. Cerebral glucose, lactate, pyruvate and glycerol were determined. In the last two animals of each group, cerebral tissue was examined by electron microscopy. RESULTS: Cerebral lactate was higher in the LP-group than the HP-group during normothermic CPB. Compared with baseline, cerebral glucose of the LP-group decreased whereas lactate/pyruvate-ratio, lactate and glycerol-concentrations increased during normothermic CPB. In the HP-group these parameters remained unchanged. Electron microscopy showed 31.2% and 8.3% altered mitochondria in the cortical micrographs taken from the LP- and the HP-group, respectively (p<0.001). CONCLUSION: MAP below 45 mmHg during CPB was associated with cerebral biochemical and morphological changes consistent with anaerobic metabolism and subcellular injury.

Elevated flow rate during cardiopulmonary bypass is associated with fluid accumulation.

OBJECTIVE: High flow rates during cardiopulmonary bypass are assumed to increase fluid accumulation. This study aimed to determine whether two different flow rates during cardiopulmonary bypass alter the intraoperative fluid balance and extravasation rate. METHODS: Sixteen pigs underwent 60 minutes of normothermic bypass, followed by 90 minutes of hypothermic bypass. A high-flow group (HF group, n = 8) had a cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) and a low-flow group (LF group, n = 8) had a rate of 80 mL x kg(-1) x min(-1). Blood chemistry, hemodynamic parameters, plasma and interstitial colloid osmotic pressure, net fluid balance, plasma volume, fluid extravasation rate, and total tissue water content were measured or calculated. Results are presented as mean (standard deviation). RESULTS: The average net fluid balance during cardiopulmonary bypass was 1.02 (0.25) and 0.73 (0.23) mL x kg(-1) x min(-1) in the HF group and LF group, respectively (P < .05). The average fluid extravasation rate was 0.98 (0.22) and 0.77 (0.22) mL x kg(-1) x min(-1) in the HF group and the LF group (P = .07). Total water content was higher in the kidneys (P < .05) and tended to be higher in the lungs (P = .05), liver (P = .07), and brain (P = .07) of the HF group than in those of the LF group. The between-group differences in net fluid balance and fluid extravasation rate were present during the first 30 minutes of normothermic cardiopulmonary bypass. Thereafter, the values stabilized and remained similar in the two groups. Plasma volume and systemic vascular resistance differed between the groups. CONCLUSION: Cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) was associated with higher positive net fluid balance and fluid extravasation rate than 80 mL x kg(-1) x min(-1). The effect was mainly observed in the initial phase of cardiopulmonary bypass.

Intraoperative fluid balance during cardiopulmonary bypass: effects of different mean arterial pressures.

INTRODUCTION: This study investigated whether two levels of mean arterial pressure (MAP) during cardiopulmonary bypass did influence per-operative fluid shifts. METHODS: Sixteen pigs underwent 60 minutes of normothermic cardiopulmonary bypass (CPB) followed by 90 minutes of hypothermic CPB. Eight animals had a MAP of 60-80mmHg by norepinephrine (HP group). Another 8 animals had a MAP of 40-45 mmHg by phentolamine (LP group). Blood chemistry, plasma/interstitial colloid osmotic pressures, plasma volume, fluid balance, fluid extravasation rate and tissue water content were measured or calculated. RESULTS: The plasma volume was significantly lower in the HP group compared with the LP group after 60 minutes of CPB. Net fluid balance was 0.18 (0.05) ml x kg(-1) x min(-1) in the HP group and 0.21 ml x kg(-1) x min(-1) in the LP group (P > 0.05) while fluid extravasation rate was 1.18 (0.5) and 1.13 (0.4) ml x kg(-1) x min(-1) in the HP group and the LP group during CPB (P > 0.05). CONCLUSION: Net fluid balance and fluid extravasation rate were similar in the animals with elevated and with lowered MAP during CPB.

Mean arterial pressure about 40 mmHg during CPB is associated with cerebral ischemia in piglets.

OBJECTIVE: To investigate if a mean arterial pressure below 50 mmHg during CPB may lead to cerebral ischemia. MATERIAL AND METHODS: Piglets with low mean arterial pressure by nitroprusside (LP-group) (n=6) were compared with piglets given norepinephrine to obtain high pressure (HP-group) (n=6) during normothermic and hypothermic CPB. Intracranial pressure, flow and markers of cerebral energy metabolism (microdialysis) were recorded. RESULTS: Mean arterial pressure differed significantly between the groups and stabilized about 40-45 mmHg in the LP-group. Cerebral perfusion pressure decreased to 21.3 (7.7) mmHg in the LP-group and increased to 51.8 (11.2) mmHg in the HP-group at 150 min of CPB (P<0.001, between groups). During bypass the intracerebral glucose concentration decreased significantly in the LP-group. In this group the lactate/pyruvate ratio increased from 15.5 (5.3) to 64.5 (87.6) at 90 min and 45.0 (36.5) at 150 min (P<0.05) with no such changes in the HP-group. Similarly the cerebral glycerol concentration increased significantly in the LP-group, whereas glycerol remained stable in the HP-group. CONCLUSION: Mean arterial pressure about 40 mmHg during CPB is associated with cerebral ischemia.

Time course variations of haemodynamics, plasma volume and microvascular fluid exchange following surface cooling: an experimental approach to accidental hypothermia.

OBJECTIVE: To describe how surface cooling influences fluid distribution, vascular capacity and haemodynamic variables. METHODS: Seven anaesthetised pigs, following normothermic stabilization for 60 min, were cooled to 27.8+/-1.6 degrees C. Fluid balance, haemodynamics, colloid osmotic pressures (plasma/interstitial fluid), haematocrit [s-albumin/protein] were recorded and plasma volume measured together with tissue perfusion during normothermia, cooling and stable hypothermia (coloured microspheres). Fluid shifts and changes in albumin and protein masses were calculated. At the end tissue water content was assessed. RESULTS: Haemodynamic variables changed with the start of cooling in parallel with a decreasing cardiac output. During hypothermia the haematocrit increased from 0.31+/-0.01 to 0.35+/-0.01 (P < 0.01). Plasma volume decreased from 1139.0+/-65.4 ml at start of cooling to 882.0+/-67.5 ml 3 h later (P < 0.05). In parallel the plasma albumin and protein masses decreased from 37.8+/-2.5 g and 54.6+/-4.0 g to 28.0+/-2.7 g (P < 0.05) and 41.2+/-4.1 g (P > 0.05), respectively. The main changes occurred 120-180 min after start of each experiment. In this period the fluid extravasation rate was elevated (P < 0.05) without influencing the colloid osmotic pressure of plasma/interstitial fluid. The increased fluid filtration was reflected by an increase in tissue water content. CONCLUSION: Our results are in favour of a shift of plasma from circulation to the interstitial space during surface cooling. This conclusion is based on the parallel losses of fluid and proteins from circulation with unchanged colloid osmotic pressures (plasma/interstitial fluid). Inflammation may be involved.

Outcome after acute respiratory failure is more dependent on dysfunction in other vital organs than on the severity of the respiratory failure.

INTRODUCTION: The incidence and outcome of acute respiratory failure (ARF) depend on dysfunction in other organs. As a result, reported mortality in patients with ARF is derived from a mixed group of patients with different degrees of multiorgan failure. The main goal of the present study was to investigate patient outcome in single organ ARF. PATIENTS AND METHOD: From 1 January 2000 to 1 July 2002, all adult patients (>16 years) in the intensive care unit (ICU) at Haukeland University Hospital were scored daily using the Sequential Organ Failure Assessment (SOFA) score for organ failure. ARF was defined by the SOFA criteria: ratio of arterial oxygen tension to fractional inspired oxygen, with a value < 26.6 kPa (200 mmHg) in more than one recording during the ICU stay (SOFA score 3 or 4). Patients with ARF alone and in combination with other severe organ failure (SOFA score 3 or 4) were included. Survival was recorded on discharge from the ICU, at hospital discharge and at 90 days after ICU discharge. RESULTS: During the period of study, 832 adult patients were treated and 529 (63.0%) had ARF. The ICU, hospital and 3-month mortality rates were lowest in single organ ARF (3.2, 14.7 and 21.8%, respectively), with increasing mortality with each additional organ failure. When ARF occurred with four or five additional organ failures, the 3-month mortality rate was 75%. No significant differences in mortality were found between early and late ARF. CONCLUSION: The prognosis for ICU patients with single organ ARF is good, both in the short and long terms. The high overall mortality rate observed is caused by dysfunction in other organs.