Correlation of optic nerve and optic nerve sheath diameter with intracranial pressure in pigs.

OBJECTIVE: Several studies have shown an association between intracranial pressure and the diameter of the optic nerve sheath measured by transbulbar ultrasonography. To understand the pathophysiology of this phenomenon, we aimed to measure the changes of the optic nerve, optic nerve sheath and perineural space separately with increasing intracranial pressure in a porcine model. METHODS: An external ventricular drain was placed into the third ventricle through a right paramedian burrhole in eight anesthesized pigs. The diameters of the optic nerve and the optic nerve sheath were measured while the intracranial pressure (ICP) was increased in steps of 10mmHg from baseline up to 60 mmHg. RESULTS: The median diameters of the optic nerve (ON) increased from 0.36 cm (baseline- 95% confidence interval (CI) 0.33 cm to 0.45 cm) to 0.68 cm (95% CI 0.57 cm to 0.82 cm) at ICP of 60 mmHg (p<0.0001) and optic nerve sheath (ONS) from 0.88 cm (95% CI 0.79 cm to 0.98 cm) to 1.24 cm (95% CI 1.02 cm to 1.38 cm) (p< 0.002) while the median diameter of the perineural space (PNS) (baseline diameter 95% CI 0.40 cm to 0.59 cm to diameters at ICP 60 95% CI 0.38 cm to 0.62 cm) did not change significantly (p = 0.399). Multiple comparisons allowed differentiation between baseline and values ≥40 mmHg for ON (p = 0.017) and between baseline and values ≥ 50mmHg for ONS (p = 0.006). A linear correlation between ON (R2 = 0.513, p<0.0001) and ONS (R2 = 0.364, p<0.0001) with ICP was found. The median coefficient of variation for intra- and inter-investigator variability was 8% respectively 2.3%. CONCLUSION: Unexpectedly, the increase in ONS diameter with increasing ICP is exclusively related to the increase of the diameter of the ON. Further studies should explore the reasons for this behaviour.

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines

PURPOSE: To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. METHODS: We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. RESULTS: We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. CONCLUSIONS: We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.

Neurohistological abnormalities during early porcine endotoxemia.

BACKGROUND: Brain dysfunction is common in sepsis. We aimed to assess whether cerebral perfusion, oxygenation, and/or metabolism are abnormal during early endotoxemia, and how they may relate to potential neurohistological changes. METHODS: In this prospective animal study, we included 12 pigs (weight: 42 ± 4 kg; mean ± SD) that were exposed to Escherichia coli lipopolysaccharide (E. coli LPS B0111 : B4, 0.4 µg/kg/h) or saline infusion (n = 6, each) for 10 h. Systemic hemodynamics, cerebral blood flow, intracranial pressure, and brain tissue oxygen tension were continuously measured. At the end of the experiment, formalin-fixed brains were cut in coronal sections and embedded in paraffin. Afterwards, the sections were cut at 5 microns and stained with hematoxylin and eosin. RESULTS: Stable systemic hemodynamics in both groups were associated with higher carotid arterial blood flow after 10 h of endotoxemia (9.0 ± 2.2 ml/kg/min) compared to controls (6.6 ± 1.2 ml/kg/min; time-group interaction: P = 0.014). Intracranial pressure, cerebral perfusion pressure, brain oxygen consumption, and brain tissue oxygen tension were similar in both groups. In four of the six endotoxemic animals but in none of the controls, cerebral tissue lesions were found (encephalomalacia with spongy degeneration of white matter, axonal swelling, and ischemic neuronal thalamic necrosis), including significant venous vascular alterations, predominantly in the brainstem, in three of the four animals. CONCLUSIONS: Early endotoxemia seems to be associated with histological signs of brain damage unrelated to systemic or cerebral hemodynamics or oxygenation.

Forced fluid removal in critically ill patients with acute kidney injury.

PURPOSE: The aim was to test the feasibility of protocol-driven fluid removal with continuous renal replacement therapy (CRRT) in patients in whom standard fluid balance prescription did not result in substantial negative fluid balances. MATERIALS AND METHODS: In 10 mechanically ventilated patients with sepsis or signs of inflammation and acute kidney injury [age 65 (48-78 years; median, range), simplified acute physiology score II 66 (39-116)], fluid removal was guided by mean arterial pressure (MAP), cardiac index (CI), mixed venous oxygen saturation (SvO(2)), lactate/base excess, peripheral circulation, and filling pressures, and adjusted hourly with the goal to maximize volume removal for up to 3 days. RESULTS: Fluid removal rates during the 3 days before and during the study period [66 (36-72) h] were 11 (-30 to +36) ml/kg/day and -59 (-85 to -31) ml/kg/day, respectively (P = 0.002). In 12% of a total of 594 fluid removal rate evaluations, fluid removal had to be decreased or stopped. Most frequent reasons leading to decreasing fluid removal were (n, % of all instances, median lowest value from all patients): SvO(2) (44, 28%, 59%), MAP (36, 23%, 57 mmHg), CI (26, 17%, 2.4 l/min/m(2)), low peripheral temperature (22, 14%, 'cold'). Overall, systemic hemodynamics remained stable throughout the study period. CONCLUSIONS: In these patients, protocolized fluid removal with CRRT was associated with large negative fluid balances.

Oxygen transport and mitochondrial function in porcine septic shock, cardiogenic shock, and hypoxaemia.

INTRODUCTION: The relevance of tissue oxygenation in the pathogenesis of organ dysfunction during sepsis is controversial. We compared oxygen transport, lactate metabolism, and mitochondrial function in pigs with septic shock, cardiogenic shock, or hypoxic hypoxia. METHODS: Thirty-two anaesthetized, ventilated pigs were randomized to faecal peritonitis (P), cardiac tamponade (CT), hypoxic hypoxia (HH) or controls. Systemic and regional blood flows, lactate, mitochondrial respiration, and tissue hypoxia-inducible factor 1 alpha (HIF-1α) were measured for 24 h. RESULTS: Mortality was 50% in each intervention group. While systemic oxygen consumption (VO(2) ) was maintained in all groups, hepatic VO(2) tended to decrease in CT [0.84 (0.5-1.3) vs. 0.42 (0.06-0.8)/ml/min/kg; P = 0.06]. In P, fractional hepatic, celiac trunk, and portal vein blood flows, and especially renal blood flow [by 46 (14-91)%; P = 0.001] decreased. In CT, renal blood flow [by 50.4 (23-81)%; P = 0.004] and in HH, superior mesenteric blood flow decreased [by 38.9 (16-100)%, P = 0.009]. Hepatic lactate influx increased > 100% in P and HH, and > 200% in CT (all P < 0.02). Hepatic lactate uptake remained unchanged in P and HH and converted to release in CT. Mitochondrial respiration remained normal. Muscle adenosine triphosphate (ATP) concentrations decreased in P (5.9 ± 1.4 µmol/g wt vs. 2.8 ± 2.7 µmol/g wt, P = 0.04). HIF-1α expression was not detectable in any group. CONCLUSION: We conclude that despite shock and renal hypoperfusion, tissue hypoxia is not a major pathophysiological issue in early and established faecal peritonitis. The reasons for reduced skeletal muscle tissue ATP levels in the presence of well-preserved in-vitro muscle mitochondrial respiration should be further investigated.

Assessment of pain in sedated and mechanically ventilated patients: an observational study.

BACKGROUND: Critically ill patients often undergo unpleasant procedures. We quantified the effects of an unpleasant stimulus on physiological and behavioral parameters and evaluated how they are modified by sedation and analgesia. METHODS: A 6-month study in the 30-bed intensive care unit (ICU) of a university hospital examined 21 sedated patients from various diagnostic groups. Hemodynamic and respiratory parameters, pupil size, facial expression, muscle tone, body movement, and the Richmond Agitation-Sedation Scale (RASS) score were measured before and during intratracheal suctioning, first in sedated patients, after sedation was stopped, and after an opioid bolus. RESULTS: Before intratracheal suctioning, patients had RASS scores of -1.8 ± 1.2 (mean ± standard deviation; sedation), -0.6 ± 1.7 (sedation stop), and -0.9 ± 1.4 (analgesia) (P = 0.014). Intratracheal suctioning significantly increased RASS during both sedation (to -0.6 ± 1.7) and sedation stop (to 1.0 ± 1.5) (both P < 0.01), but not during analgesia. Systolic blood pressure increased during sedation (by 9 ± 10 mmHg), during sedation stop (by 15 ± 17 mmHg) and during analgesia (by 9 ± 4 mmHg; all P < 0.01), but diastolic pressure only during sedation and sedation stop (both P < 0.01). Facial expression, body movement, and muscle tone changed significantly during the episodes of intratracheal suctioning. Heart rate, tidal volume, and pupil size remained stable under all conditions. CONCLUSIONS: Intratracheal suctioning evoked significant changes in some physiological and behavioral parameters. Some physiological changes were suppressed by analgesia, but at our ICU's standard doses, neither analgesia nor sedation attenuated changes in behavioral parameters at the intensity tested.

Effect of site of lactate infusion on regional lactate exchange in pigs.

BACKGROUND: The rate of extra-hepatic lactate production and the route of influx of lactate to the liver may influence both hepatic and extra-hepatic lactate exchange. We assessed the dose-response of hepatic and extra-hepatic lactate exchange during portal and central venous lactate infusion. METHODS: Eighteen pigs randomly received either portal (n=5) or central venous (n=7) lactate infusion or saline (n=6). Sodium lactate was infused at 33, 66, 99, and 133 µmol kg⁻¹ min⁻¹ for 20 min each. Systemic and regional abdominal blood flows and plasma lactate were measured at 20 min intervals until 1 h post-infusion, and regional lactate exchange was calculated (area under lactate uptake-time curve). RESULTS: Total hepatic lactate uptake [median (95% confidence interval)] during the experimental protocol (140 min) was higher during portal [8198 (5487-12 798) µmol kg(-1)] than during central venous lactate infusion [4530 (3903-5514) µmol kg⁻¹, P<0.05]. At a similar hepatic lactate delivery (∼400 µmol kg⁻¹ min⁻¹), hepatic lactate uptake [mean and standard deviation (sd)] was higher during portal [118 (sd 55) µmol kg⁻¹ min⁻¹] than during central venous lactate infusion [44 (12) µmol kg⁻¹ min⁻¹, P < 0.05]. Time courses of arterial lactate concentrations and lactate uptake at other measured regions were similar in both groups. CONCLUSIONS: Higher hepatic lactate uptake during portal compared with central venous lactate infusion at a similar total hepatic lactate influx underlines the role of portal vein lactate concentration in total hepatic lactate uptake capacity. Arterial lactate concentration does not depend on the site of lactate infusion. At higher arterial lactate concentrations, all regions participated in lactate uptake.

The association between early hemodynamic variables and outcome in normothermic comatose patients following cardiac arrest.

BACKGROUND: Currently, few data exist on the association between post-cardiac arrest hemodynamic function and outcome. In this explorative, retrospective analysis, the association between hemodynamic variables during the first 24 h after intensive care unit admission and functional outcome at day 28 was evaluated in 153 normothermic comatose patients following a cardiac arrest. METHODS: Medical records of a multidisciplinary intensive care unit were reviewed for comatose patients (Glasgow Coma Scale < or = 9) admitted to the intensive care unit after successful resuscitation from an in- or an out-of-hospital cardiac arrest. The hourly variable time integral of hemodynamic variables during the first 24 h after admission was calculated. At day 28, outcome was assessed as favorable or adverse based on a Cerebral Performance Category of 1-2 and 3-5, respectively. Bi- and multivariate regression models adjusted for relevant confounding variables were used to evaluate the association between hemodynamic variables and functional outcome. RESULTS: One hundred and fifty-three normothermic comatose patients were admitted after a cardiac arrest, of whom 64 (42%) experienced a favorable outcome. Neither in the adjusted bivariate models (r(2), 0.61-0.78) nor in the adjusted multivariate model (r(2), 0.62-0.73) was the hourly variable time integral of any hemodynamic variable during the first 24 h after intensive care unit admission associated with functional patient outcome at day 28 in all patients as well as in patients after an in- or an out-of-hospital cardiac arrest. CONCLUSION: Commonly measured hemodynamic variables during the first 24 h following intensive care unit admission due to a cardiac arrest do not appear to be associated with the functional outcome at day 28.

Time- and dose-related regional fluxes of tissue-type plasminogen activator in anesthetized endotoxemic pigs.

BACKGROUND: Acute endotoxinemia elicits an early fibrinolytic response. This study analyzes the effects of the dose and duration of endotoxin infusion on arterial levels of tissue-type plasminogen activator (tPA) and pulmonary, mesenteric and hepatic plasma tPA fluxes. METHODS: Pigs were randomized to receive an acute, high-dose (for 6 h, n=13, high ETX) or a prolonged, low-dose (for 18 h, n=18, low ETX) infusion of endotoxin or saline vehicle alone (for 18 h, n=14, control). All animals were fluid resuscitated to maintain a normodynamic circulation. Systemic and regional blood flows were measured and arterial, pulmonary arterial, portal and hepatic venous blood samples were analyzed to calculate regional net fluxes of tPA. Plasma tumor necrosis factor (TNF-alpha) levels were analyzed. RESULTS: Mesenteric tPA release and hepatic uptake increased maximally at 1.5 h in ETX groups related to dose. Maximal mesenteric tPA release [high ETX 612 (138-1185) microg/min/kg, low ETX 72 (32-94) microg/min/kg, median+/-interquartile range] and hepatic tPA uptake [high ETX -1549 (-1134 to -2194) microg/min/kg, low ETX -153 (-105 to -307) microg/min/kg] correlated to TNF-alpha levels. Regional tPA fluxes returned to baseline levels at 6 h in both ETX groups and also remained low during sustained low ETX. No changes were observed in control animals. CONCLUSIONS: Endotoxemia induces an early increase in mesenteric tPA release and hepatic tPA uptake related to the severity of endotoxemia. The time patterns of changes in mesenteric and hepatic tPA fluxes are similar in acute high-dose endotoxemia and sustained low-dose endotoxemia.

The influence of local and systemic preconditioning on oxygenation, metabolism and survival in critically ischaemic skin flaps in pigs.

Stress proteins represent a group of highly conserved intracellular proteins that provide adaptation against cellular stress. The present study aims to elucidate the stress protein-mediated effects of local hyperthermia and systemic administration of monophosphoryl lipid A (MPL) on oxygenation, metabolism and survival in bilateral porcine random pattern buttock flaps. Preconditioning was achieved 24h prior to surgery by applying a heating blanket on the operative site (n = 5), by intravenous administration of MPL at a dosage of 35 microg/kg body weight (n = 5) or by combining the two (n = 5). The flaps were monitored with laser Doppler flowmetry, polarographic microprobes and microdialysis until 5h postoperatively. Semiquantitative immunohistochemistry was performed for heat shock protein 70 (HSP70), heat shock protein 32 (also termed haem oxygenase-1, HO-1), and inducible nitrc oxide synthase (iNOS). The administration of MPL increased the impaired microcirculatory blood flow in the proximal part of the flap and partial oxygen tension in the the distal part by approximately 100% each (both P<0.05), whereas both variables remained virtually unaffected by local heat preconditioning. Lactate/pyruvate (L/P) ratio and glycerol concentration (representing cell membrane disintegration) in the distal part of the flap gradually increased to values of approximately 500 mmol/l and approximately 350 micromol/l, respectively (both P<0.01), which was substantially attenuated by heat application (P<0.01 for L/P ratio and P<0.05 for glycerol) and combined preconditioning (P<0.01 for both variables), whereas the effect of MPL was less marked (not significant). Flap survival was increased from 56% (untreated animals) to 65% after MPL (not significant), 71% after heat application (P<0.05) and 78% after both methods of preconditioning (P<0.01). iNOS and HO-1 were upregulated after each method of preconditioning (P<0.05), whereas augmented HSP70 staining was only observed after heat application (P<0.05). We conclude that local hyperthermia is more effective in preventing flap necrosis than systemic MPL administration because of enhancing the cellular tolerance to hypoxic stress, which is possibly mediated by HSP70, whereas some benefit may be obtained with MPL due to iNOS and HO-1-mediated improvement in tissue oxygenation.

Practical sources of error in measuring pulmonary artery occlusion pressure: a study in participants of a special intensivist training program of The Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI).

BACKGROUND: Physiological data obtained with the pulmonary artery catheter (PAC) are susceptible to errors in measurement and interpretation. Little attention has been paid to the relevance of errors in hemodynamic measurements performed in the intensive care unit (ICU). The aim of this study was to assess the errors related to the technical aspects (zeroing and reference level) and actual measurement (curve interpretation) of the pulmonary artery occlusion pressure (PAOP). METHODS: Forty-seven participants in a special ICU training program and 22 ICU nurses were tested without pre-announcement. All participants had previously been exposed to the clinical use of the method. The first task was to set up a pressure measurement system for PAC (zeroing and reference level) and the second to measure the PAOP. RESULTS: The median difference from the reference mid-axillary zero level was - 3 cm (-8 to + 9 cm) for physicians and -1 cm (-5 to + 1 cm) for nurses. The median difference from the reference PAOP was 0 mmHg (-3 to 5 mmHg) for physicians and 1 mmHg (-1 to 15 mmHg) for nurses. When PAOP values were adjusted for the differences from the reference transducer level, the median differences from the reference PAOP values were 2 mmHg (-6 to 9 mmHg) for physicians and 2 mmHg (-6 to 16 mmHg) for nurses. CONCLUSIONS: Measurement of the PAOP is susceptible to substantial error as a result of practical mistakes. Comparison of results between ICUs or practitioners is therefore not possible.

Pulmonary capillary pressure. A review.

Pulmonary capillary pressure (Pcap) is the predominant force that drives fluid out of the pulmonary capillaries into the interstitium. Increasing hydrostatic capillary pressure is directly proportional to the lung's transvascular filtration rate, and in the extreme leads to pulmonary edema. In the pulmonary circulation, blood flow arises from the transpulmonary pressure gradient, defined as the difference between pulmonary artery (diastolic) pressure and left atrial pressure. The resistance across the pulmonary vasculature consists of arterial and venous components, which interact with the capacitance of the compliant pulmonary capillaries. In pathological states such as acute respiratory distress syndrome, sepsis, and high altitude or neurogenic lung edema, the longitudinal distribution of the precapillary arterial and the postcapillary venous resistance varies. Subsequently, the relationship between Pcap and pulmonary artery occlusion pressure (PAOP) is greatly variable and Pcap can no longer be predicted from PAOP. In clinical practice, PAOP is commonly used to guide fluid therapy, and Pcap as a hemodynamic target is rarely assessed. This approach is potentially misleading. In the presence of a normal PAOP and an increased pressure gradient between Pcap and PAOP, the tendency for fluid leakage in the capillaries and subsequent edema development may substantially be underestimated. Tho-roughly validated methods have been developed to assess Pcap in humans. At the bedside, measurement of Pcap can easily be determined by analyzing a pressure transient after an acute pulmonary artery occlusion with the balloon of a Swan-Ganz catheter.

Oxygen extraction in pigs subjected to low-dose infusion of endotoxin after major abdominal surgery.

BACKGROUND: Sepsis may impair O(2) extraction due to blood flow redistribution or decreased utilization of the available oxygen. METHODS: We assessed the effect of endotoxemia on systemic and regional O(2) extraction and lactate handling in pigs, randomized to receive either endotoxin (0.4 microg kg(-1) h(-1); n = 10) or saline infusion (controls; n = 9) for 12 h. RESULTS: High baseline regional and systemic O(2) extraction in the endotoxin group (median 56%, range 45-77%) and in the controls (67%, 49-72%) was maintained until the end of the experiment (endotoxin group: 60%, 50-71%; controls: 60%, 50-74%) despite hypotension and a decrease in stroke volume in endotoxic animals. Hepatic lactate exchange decreased during endotoxemia from 14 micromol kg(-1) min(-1) (range 10-28 micromol kg(-1) min(-1)) to 10 (range 3-15) micromol kg(-1) min(-1); P < 0.01), but remained stable in the controls, with 13 micromol min(-1) (4-18 micromol min(-1)) at baseline and 7 micromol min(-1) (3-17 micromol min(-1)) after 12 h of saline infusion. CONCLUSIONS: The high and sustained oxygen consumption and oxygen extraction in this endotoxemic model speak against any major impairment of hepatosplanchnic or systemic oxygen extraction and oxidative metabolism. The reduced hepatic lactate exchange despite an unchanged hepatic lactate influx suggests altered metabolic activities independent of oxygen consumption.

Lack of effect of ranitidine on gastric luminal pH and mucosal PCO2 during the first day in the ICU.

BACKGROUND: Histamine(2) (H(2))-blocking agents can attenuate intragastric CO(2)-production by reducing gastric acid secretion and preventing the interaction between H(+) and bicarbonate. However, gastric acid production may be impaired in acute circulatory failure due to poor mucosal perfusion, and H(2)-blockade could further impair mucosal perfusion. METHODS: Forty patients with acute circulatory and/or respiratory failure, age 61 +/- 16 years (mean +/- SD), APACHE II score 21 +/- 7, and SOFA score 8 +/- 3, received randomly either ranitidine, 50 mg (R) or placebo (P) every 8 h. Gastric intraluminal pH (gpH; antimony probe with external reference electrode) and mucosal pCO(2) (prCO(2), semicontinuous air-tonometry) were measured during 24 h, and blood gases were taken at 6-h intervals. RESULTS: Gastric intraluminal pH was 4.3 +/- 2.4 in P and 5.1 +/- 1.6 in R (NS). Mean prCO(2) was 6.8 +/- 2.7 kPa in P and 7.4 +/- 2.1 kPa in R, and mucosal-arterial pCO(2) gradient (Delta pCO(2)) was 2.2 +/- 2.9 kPa and 2.4 +/- 2.4 kPa, respectively (NS). Within-patient variabilities of gpH and prCO(2) were not influenced by ranitidine. A posthoc analysis revealed that non-survival in R was associated with a low mucosal pHi after 24 h (P = 0.002). This was explained by a low arterial pH but not by differences in gpH or prCO(2). CONCLUSION: In acute respiratory and circulatory failure, H(2) blockade has an inconsistent impact on gpH and does not reduce variabilities of gpH or prCO(2).

Improved skin flap survival after local heat preconditioning in pigs.

BACKGROUND: Preconditioning induces the expression of heat shock proteins (HSPs), which can help a cell survive an acute episode of stress. Similar to the induction of HSP expression, the cell protection is independent of the type of stress. The aim of this study was to test in a large, randomized animal model, if skin flap survival may be improved by local heat preconditioning and induction of HSP 70. MATERIALS AND METHODS: Twenty-four hours before surgery, a heating blanket was laid on the buttocks of large white pigs. In the preconditioned group (n = 6), the blanket was warmed up to 43 degrees C for 3 x 30 min, whereas it was kept at room temperature in between the heating episodes as well as in the control animals (n = 6). A random pattern skin flap was raised on both sides of the buttocks. Flap survival was measured clinically. Induction of HSP and apoptosis were assessed quantitatively by immunohistochemistry and TUNEL assay, respectively. RESULTS: Preconditioning reduced flap necrosis from 40 +/- 8% of the total flap surface to 7 +/- 14% (P < 0.01). Induction of HSP was significantly higher in the experimental group (79 +/- 12% versus 42 +/- 13%, P < 0.01), whereas apoptosis in healthy flap tissue was reduced from 30 +/- 11 to 11 +/- 6 cells/visual field (P < 0.01). CONCLUSION: In the present study, necrosis and apoptosis rate of skin flaps could be reduced significantly due to local heat preconditioning. Our results suggest that ischemia-related wound healing complications could be diminished with local heat application, a most simple and least invasive method of preconditioning.

Prevention of acute renal failure--fluid repletion and colloids.

Hypovolemia alone or in conjunction with other factors is a main reason for acute renal failure in critically ill patients. Various crystalloid and colloid solutions are available to correct hypovolemia. Some of them have been implicated in impairment of renal function. Infusion of large amounts of sodium chloride is associated with increased incidence of nausea, vomiting and hyperchloremic metabolic acidosis. While gelatins and HES are preferred colloids in patients with normal kidney function, there is some evidence that the latter are associated with impaired renal function in patients with pre-existing kidney disease. Any hyperoncotic colloid given in large amounts may decrease glomerular filtration, and should therefore be combined with crystalloids.

Splanchnic perfusion during hemodialysis: evidence for marginal tissue perfusion.

OBJECTIVE: Splanchnic perfusion may be compromised during hemodialysis because of hypovolemia, inflammatory response, and blood flow redistribution. The aim of this study was to assess the response of splanchnic blood flow and oxygen transport to hemodialysis. DESIGN: A prospective clinical study. SETTING: A mixed medical-surgical intensive care unit in a university hospital. PATIENTS: Nine patients with acute renal failure. INTERVENTIONS: A 4-hr period of hemodialysis. MEASUREMENTS AND MAIN RESULTS: Systemic (via a pulmonary artery catheter), hepatosplanchnic, and femoral (via dye dilution) blood flow and gastric mucosal Pco2 were measured before, during, and 2 hrs after hemodialysis. During hemodialysis, despite unchanged arterial blood pressure, cardiac output and stroke volume decreased from 3.0 +/- 1.0 L/m2/min (mean +/- sd) to 2.3 +/- 0.7 L/m2/min (p =.02), and from 38 +/- 16 mL/m2/min to 28 +/- 12 mL/m2/min (p =.01), respectively. Splanchnic but not femoral blood flow decreased from 0.9 +/- 0.3 L/m2/min to 0.7 +/- 0.2 L/m2/min (p =.02). The blood flows returned to baseline values after dialysis without need for therapeutic interventions. Gastric mucosal-arterial Pco2 gradients were high before dialysis (35 +/- 23 torr [4.6 +/- 3.1 kPa]) and did not change. Renin but not atrial natriuretic peptide concentration increased during hemodialysis from 13 +/- 13 microg/L to 35 +/- 40 microg/L and decreased afterward to baseline values (13 +/- 13 microg/L; p =.01). Whereas interleukin 6 tended to decrease, tumor necrosis factor alpha increased during hemodialysis from 74 +/- 24 pg/mL to 86 +/- 31 pg/mL and continued to increase after hemodialysis to 108 +/- 66 pg/mL (p =.022). CONCLUSION: Hemodialysis and fluid removal in normotensive patients with acute renal failure may result in a reduction of systemic and splanchnic blood flow that is undetectable using traditional clinical signs. In contrast to what is observed in hypovolemia, the changes in regional blood flow are rapidly reversible after hemodialysis.

Effects of systemic arterial hypoperfusion on splanchnic hemodynamics and hepatic arterial buffer response in pigs.

The hepatic arterial buffer response (HABR) tends to maintain liver blood flow under conditions of low mesenteric perfusion. We hypothesized that systemic hypoperfusion impairs the HABR. In 12 pigs, aortic blood flow was reduced by cardiac tamponade to 50 ml. kg(-1). min(-1) for 1 h (short-term tamponade) and further to 30 ml. kg(-1). min(-1) for another hour (prolonged tamponade). Twelve pigs without tamponade served as controls. Portal venous blood flow decreased from 17 +/- 3 (baseline) to 6 +/- 4 ml. kg(-1). min(-1) (prolonged tamponade; P = 0.012) and did not change in controls, whereas hepatic arterial blood flow decreased from 2 +/- 1 (baseline) to 1 +/- 1 ml. kg(-1). min(-1) (prolonged tamponade; P = 0.050) and increased from 2 +/- 1 to 4 +/- 2 ml. kg(-1). min(-1) in controls (P = 0.002). The change in hepatic arterial conductance (DeltaC(ha)) during acute portal vein occlusion decreased from 0.1 +/- 0.05 (baseline) to 0 +/- 0.01 ml. kg(-1). min(-1). mmHg(-1) (prolonged tamponade; P = 0.043). In controls, DeltaC(ha) did not change. Hepatic lactate extraction decreased, but hepatic release of glutathione S-transferase A did not change during cardiac tamponade. In conclusion, during low systemic perfusion, the HABR is exhausted and hepatic function is impaired without signs of cellular damage.