Efficacy of pressure support ventilation dependent on extravascular lung water.

Continuous positive-pressure ventilation and PSV were compared prospectively in patients at a surgical intensive care unit. All patients suffered from mild to moderate ARI (PaO2/FIO2 of 125 to 350 mm Hg). The patients were randomly assigned to a PSV group (n = 28) or a control group with continued CPPV (n = 27). The usual hemodynamic and oxygenation variables, ITBV, and extravascular lung water (ETV) were assessed before and six hours after switching to PSV. The changes (d) of PaO2/FIO2, RI, and P(A-a)O2 were used for evaluation of the effect of PSV. Significant correlations were found between the ETV(CPPV) and dPaO2/FIO2 (r = -0.672), ETV(CPPV) and dRI (r = 0.722), and ETV(CPPV) and dP(A-a)O2 (r = 0.601), which led to the conclusion that the level of ETV determined the efficacy of PSV. In the subgroup with ETV less than 11 ml/kg (n = 15), PSV significantly improved PaO2/FIO2 (248 to 286 mm Hg), RI (1.55 to 1.22), ITBV (801 to 888 ml/m2), cardiac index (4.21 to 4.76 L/min.m2), stroke index (42.2 to 48.1 ml/m2), and oxygen delivery (735 to 833 ml/min.m2). In the subgroup with ETV greater than 11 ml/kg (n = 13), PSV caused a significant deterioration of PaO2/FIO2, RI, and intrapulmonary shunt. It is concluded that in patients with moderate ARI in whom ETV is almost normal, PSV is superior to CPPV, and the efficacy of PSV is independent of the level of oxygenation during CPPV.

Hemodynamic monitoring by double-indicator dilution technique in patients after orthotopic heart transplantation.

STUDY OBJECTIVES: A transpulmonary thermal-dye dilution (TDD) technique using cold indocyanine green dye was utilized to monitor cardiac index (CI) and preload in patients after heart transplantation. Preload, determined by intrathoracic blood volume index (ITBVI) and global end-diastolic volume index (GEDVI), was compared to central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP) and was correlated with stroke volume index (SVI). DESIGN: Prospective study. SETTING: Cardiac surgery ICU at a university hospital. PATIENTS: Forty patients (34 men, 6 women) with a mean (+/- SD) age of 54.4+/-8.5 years after orthotopic heart transplantation. MEASUREMENTS AND RESULTS: CI and preload measurements were performed with TDD and pulmonary artery catheters in the ICU at 3, 6, 12, 24, 36, 48, and 72 h postoperatively. The femoral artery CI was compared with the pulmonary artery CI. Changes in the ITBVI, GEDVI, CVP, and PAOP were correlated with changes in the SVI. No difference was found between the femoral and pulmonary arterial CIs (r = 0.98 [bias, 0.35 L/min/m(2)]; p<0.01). There was no statistically significant correlation between changes in the SVI and changes in CVP (r = -0.23,) and PAOP (r = -0.06). However, the ITBVI (r = 0.65; p<0.01) and the GEDVI (r = 0.73; p<0.01) were significantly correlated to changes in the SVI. Changes in the same direction occurred between the SVI and the GEDVI as well as between the SVI and the ITBVI in 76.3% and 71.9% of patients, respectively, while CVP and PAOP also changed in the same direction as SVI in only 35.1% and 36.9% of patients, respectively. CONCLUSION: ITBVI and GEDVI are more reliable preload parameters than CVP and PAOP. Even in denervated hearts, ITBVI and GEDVI show significant correlations with SVI. The transpulmonary indicator dilution technique is promising and should be investigated further.

Intrathoracic blood volume accurately reflects circulatory volume status in critically ill patients with mechanical ventilation.

Positive pressure ventilation in patients with acute respiratory failure (ARF) may render the interpretation of central venous pressure (CVP) or pulmonary wedge pressure (PCWP) difficult as indicators of circulating volume. The preload component of cardiac (CI) and stroke index (SI) is also influenced by the increased intrathoracic pressures of positive pressure ventilation. Moreover CI and SI do not indicate volume status exclusively but also contractility and afterload. We investigated whether intrathoracic blood volume (ITBV) more accurately reflects blood volume status and the resulting oxygen transport (DO2). CVP, PCWP, cardiac (CI) and stroke index (SI) were measured, oxygen transport index (DO2I) and oxygen consumption index (VO2I) were calculated in 21 ARF-patients. Ventilatory patterns were adjusted as necessary. CI, SI and intrathoracic blood volume index (ITBVI) were derived from thermal dye dilution curves which were detected with a 5 F fiberoptic thermistor femoral artery catheter and fed into a thermal-dye-computer. All data were collected in intervals of 6 h. There were 224 data sets obtained. Linear regression analysis was performed between absolute values as well as between the 6 changes (prefix delta).(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring of right ventricular function using a conventional slow response thermistor catheter.

OBJECTIVE: To investigate whether determination of right ventricular end-diastolic volume (RVEDV) and right ventricular ejection fraction (RVEF) can be performed with reasonable accuracy and reproducibility using a conventional slow response thermistor pulmonary artery catheter (CPAC) applying an adaptive algorithm. DESIGN: To study RVEDV and RVEF simultaneously with pulmonary artery catheters equipped with slow and fast response thermistors (FRPAC) under a broad range of cardiac output. SETTING: Laboratory of Institute of Experimental Surgery, Technical University. ANIMALS: 11 anaesthetised piglets. INTERVENTIONS: Hypovolemia (V-) was induced by withdrawal of blood up to 50 ml/kg, hypervolemia (V+) was produced by retransfusing blood and adding up to 30 mg/kg hydroxyethyl starch. In 5 animals in phases V- and V+ beta-adrenergic stimulation was achieved with dobutamine. Finally pulmonary artery hypertension was induced by infusion of small air bubbles. MEASUREMENTS AND RESULTS: Cardiac output (CO), RVEDV and RVEF were determined simultaneously with FRPAC and CPAC placed in the same pulmonary artery branch. Measurements were repeated 8 times sequentially in steady state normovolemia. A total of 130 measurements could be analysed. The coefficient of variation was 6.7 +/- 4.2% for CO(FRPAC) and 4.6 +/- 1.7% for CO(CPAC); for RVEF it was 9.7 +/- 6.2% (FRPAC) and 9.9 +/- 3.9% (CPAC); for RVEDV it was 11.6 +/- 4.8% (FRPAC) and 8.54 +/- 3.2 (CPAC). Mean difference (bias) was 0.06 +/- 0.39 l/min for CO measured with both methods, 19 +/- 35 ml for RVEDV and -3.3 +/- 6.5% for RVEF. CO(CPAC) displayed a strong correlation to CO(FRPAC) (R = 0.97, p = 0.001) as well as RVEF (R for RVEF(CPAC) versus RVEF(FRPAC) = 0.90, p = 0.001). R for RVEDV(CPAC) versus RVEDV(FRPAC) was 0.67, p = 0.001. We conclude that this animal study demonstrates good agreement between RVEF and RVEDV obtained with catheters equipped with a fast response thermistor or with a conventional slow response thermistor allowing accurate monitoring of right ventricular function with a conventional pulmonary artery catheter.

Assessment of cardiac preload and extravascular lung water by single transpulmonary thermodilution.

OBJECTIVE: Transpulmonary double-indicator dilution is a useful monitoring technique for measurement of intrathoracic blood volume (ITBV) and extravascular lung water (EVLW). In this study, we compared a simpler approach using single arterial thermodilution derived measurements of ITBV and EVLW with the double-indicator dilution technique. DESIGN: Prospective observational clinical study. SETTING: Surgical intensive care units of two university hospitals. PATIENTS AND METHODS: Global end-diastolic volume (GEDV) derived from single thermodilution was used for calculation of ITBV. Structural regression analysis of the first two thermo-dye dilution measurements in a derivation population of 57 critically ill patients (38 male, 19 female, 18-79 years, 56 +/- 15 years) revealed ITBV = (1.25 x GEDV)-28.4 (ml). This equation was then applied to all first measurements in a validation population of 209 critically ill patients (139 male, 70 female, 10-88 years, mean 53 +/- 19 years), and single-thermodilution ITBV (ITBV(ST)) and EVLW (EVLW(ST)) was calculated and compared to thermo-dye dilution derived values (ITBV(TD), EVLW(TD)). For inter-individual comparison, absolute values for ITBV and EVLW were normalised as indexed by body surface area (ITBVI) and body weight (EVLWI), respectively. MEASUREMENTS AND RESULTS: Linear regression analysis yielded a correlation of ITBVI(ST) = (1.05 x ITBVI(TD))-58.0 (ml/m2), r = 0.97, P < 0.0001. Bias between ITBVI(TD) and ITBVI(ST) was 7.6 (ml/m2) with a standard deviation of 57.4 (ml/m2). Single-thermodilution EVLWI (EVLWI(ST)) was calculated using ITBVI(ST) and revealed the correlation EVLWI(ST) = (0.83 x EVLWI(TD)) + 1.6 (ml/kg), r = 0.96, P < 0.0001. Bias between EVLWI(TD) and EVLWI(ST) was -0.2 (ml/kg) with a standard deviation of 1.4 (ml/kg). In detail, EVLWI(ST) systematically overestimated EVLWI(TD) at low-normal values for EVLWI and underestimated EVLWI at higher values (above 12 ml/kg). CONCLUSION: Determinations of ITBV and EVLW by single thermodilution agreed closely with the corresponding values from the double-indicator technique. Since transpulmonary single thermodilution is simple to apply, less invasive and cheaper, all these features make it a promising technique for the bedside. Nevertheless, further validation studies are needed in the future.

Central venous pressure, pulmonary artery occlusion pressure, intrathoracic blood volume, and right ventricular end-diastolic volume as indicators of cardiac preload.

PURPOSE: Central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP) and right ventricular end-diastolic volume (RVEDV) are often regarded as indicators of both circulating blood volume and cardiac preload. to evaluate these relationships, the response of each variable to induced volume shifts was tested. The relationships between these variables and cardiac index (CI) and stroke volume index (SVI) was also recorded to assess the utility of each variable as an indicator of cardiac preload. The responses of the new variable intrathoracic blood volume (ITBV) to the same maneuvers was also tested. To examine the effects of changes in cardiac output alone on ITBV, the effects of infusing dobutamine were studied. MATERIALS AND METHODS: Ten anesthetized piglets were studied during conditions of normovolemia, hypovolemia, and hypervolemia. The effects of an infusion of dobutamine were examined under normovolemia and hypovolemia. Cardiac output was measured by thermo-dilution, and ITBV was measured by double-indicator dilution. RESULTS: CI was correlated to CVP with r2 = .42 (P < or = .01), to PAOP with r2 = .43 (P < or = .01), to RVEDV index with r2 = .21 (P < or = .01), and to ITBV with r2 = .78 (P < or = .01) (pooled absolute values). Bias (mean difference of the percent changes with normovolemia = 100%) +/- 1 SD; for SVI - ITBV index was 1 +/- 22%, for SVI - CVP it was -128 +/- 214%; for SVI - PAOP it was -36 +/- 46%; and for SVI - RVEDV index it was 1 +/- 29%. Dobutamine infusion increased heart rate (to about 190 x min-1 and CI by 30% in normovolemia and hypovolemia, while ITBV remained basically unchanged. CONCLUSIONS: Under the experimental conditions chosen neither CVP, PAOP, nor RVEDV reliably indicated changes in circulating blood volume, nor were they linearly and tightly correlated to the resulting changes in SVI. ITBV reflected both changes in volume status and the resulting alteration in cardiac output. The possibility that ITBV might be cardiac output-dependent was not supported. ITBV, therefore, shows potential as a clinically useful indicator of overall cardiac preload.

A clinical randomized study on the effects of invasive monitoring on burn shock resuscitation.

BACKGROUND: Ever since Charles Baxter's recommendations the standard regime for burn shock resuscitation remains crystalloid infusion at a rate of 4 ml/kg/% burn in the first 24h following the thermal injury. A growing number of studies on invasive monitoring in burn shock, however, have raised a debate regarding the adequacy of this regime. The purpose of this prospective, randomised study was to compare goal-directed therapy guided by invasive monitoring with standard care (Baxter formula) in patients with burn shock. PATIENTS AND METHODS: Fifty consecutive patients with burns involving more than 20% body surface area were randomly assigned to one of two treatment groups. The control group was resuscitated according to the Baxter formula (4 ml/kg BW/% BSA burn), the thermodilution (TDD) group was treated according to a volumetric preload endpoint (intrathoracic blood volume) obtained by invasive haemodynamic monitoring. RESULTS: The baseline characteristics of the two treatment groups were similar. Fluid administration in the initial 24h after burn was significantly higher in the TDD treatment group than in the control group (P = 0.0001). The results of haemodynamic monitoring showed no significant difference in preload or cardiac output parameters. Signs of significant intravasal hypovolemia as indicated by subnormal values of intrathoracic and total blood volumes were present in both treatment groups. Mortality and morbidity were independent on randomisation. CONCLUSION: Burn shock resuscitation due to the Baxter formula leads to significant hypovolemia during the first 48 h following burn. Haemodynamic monitoring results in more aggressive therapeutic strategies and is associated with a significant increase in fluid administration. Increased crystalloid infusion does not improve preload or cardiac output parameters. This may be due to the fact that a pure crystalloid resuscitation is incapable of restoring cardiac preload during the period of burn shock.

Early life environment determines the development of adult phobic-like fear responses in BALB/cAnN mice.

Environmental factors may unleash genetically determined susceptibility to psychopathology. Great effort has been spent in identifying both the genetic basis and environmental sources of exaggerated fear in animal models of anxiety disorders. Here, we show that the origin of inbred mice, probably via subtle differences in breeding and rearing conditions, may have large consequences specifically on acquisition and retention of fear memories, while leaving anxiety-related behaviours unaffected. These effects could be seen in BALB/cAnN (BALB), but not in C57BL/6N (C57BL/6) mice, thus suggesting their dependency on the genetic background. Increased susceptibility for developing exaggerated fear responses was accompanied by decreased long-term depression and increased surface trafficking of the AMPA receptor GluR1 subunit at the level of the basolateral amygdala complex. Together, these data raise a novel caveat in the debate about the origins of variation in behavioural studies with experimental animals. Considering that there are currently no animal models which explicitly consider conceptual analogy to the specific gene-environment interactions observed in the aetiology of phobias, our study might suggest a novel approach and direction for further preclinical studies focusing on such aspects of phobic-like fears.

Efficacy of high frequency ventilation combined with volume controlled ventilation in dependency of extravascular lung water.

In a prospective study continuous positive pressure ventilation (CPPV) was compared with the combination of CPPV and high frequency ventilation (CHFV). Forty-seven patients of a surgical intensive care unit who required mechanical ventilation were randomly assigned to a CHFV group (n = 27) or a control group with CPPV (n = 20). Usual hemodynamic and oxygenation variables, intrathoracic blood volume (ITBV) and extravascular lung water (ETV) were assessed before and 6 h after switching to CHFV (CHFV group) or maintaining CPPV (control group). In both groups mean airway pressure (MPaw) was kept constant. The change of the respiratory index (dRI) was used for evaluation of the effect of the ventilation mode. A negative correlation was found between ETV and dRI (r = -0.67), which led to the conclusion that the height of ETV determines the efficacy of CHFV. In a CHFV subgroup with ETV greater than 15 ml/kg (n = 17), CHFV significantly improved PaO2/FiO2 (18.7 to 26.4 kPa), RI (4.44 to 2.99) and intrapulmonary shunt (33.5 to 27.5%) and slightly, but significantly impaired cardiac index (CI, 4.45 to 3.92 l/min.m2), stroke volume index (40.7 to 36.4 ml/m2) and pulmonary vascular resistance index (PVRI, 310 to 366 dyn.s.cm-5.m2), but oxygen delivery (DO2) remained almost unchanged. The CI decrease came about with an increase of PVRI on account of an increased lung volume under CHFV in this group. CHFV induced no significant effects in the subgroup with ETV less than 15 ml/kg (n = 10). There were no differences in any variable during CPPV between the CHFV subgroups and corresponding subgroups of the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Accuracy and reproducibility of the measurement of actively circulating blood volume with an integrated fiberoptic monitoring system.

OBJECTIVE: Bedside monitoring of circulating blood volume has become possible with the introduction of an integrated fiberoptic monitoring system that calculates blood volume from the changes in blood concentration of indocyanine green dye 4 mins after injection. The aim of this investigation was to compare the blood volume estimate of the integrated fiberoptic monitoring system (group 1) with the standard methods of blood volume measurement using Evans blue (group 2), and indocyanine green measured photometrically (group 3). DESIGN: Prospective laboratory study. SETTING: Animal laboratory of a University's institute for experimental surgery. SUBJECTS: Eleven anesthetized, paralyzed, and mechanically ventilated piglets. INTERVENTIONS: A central venous catheter was used for the injection of the indicator dyes (Evans blue and indocyanine green). A fiberoptic thermistor catheter was advanced into the thoracic aorta. The fiberoptic catheter detects indocyanine green by reflection densitometry for the estimation of blood volume of the integrated fiberoptic monitoring system. Samples for the determination of Evans blue and indocyanine green concentrations were drawn from an arterial catheter in the femoral artery over a period of 17 mins after injection. MEASUREMENTS AND MAIN RESULTS: Measurements were performed during normovolemia, hypovolemia (blood withdrawal of < or = 30 mL/kg), and hypervolemia (retransfusion of the withdrawn blood plus an infusion of 10% hydroxyethyl starch [45 mL/kg]). Linear regression, correlation, and bias were calculated for the comparison of the blood volume estimates by the fiberoptic monitoring system (group 1) vs. the total blood volume estimates using Evans blue (group 2) and indocyanine green (group 3): group 1 = 0.82.group 2-26 mL; r2 = 82.71%; r = .91; n = 40; group 1-group 2 +/- 1 SD = -435 +/- 368 mL; group 1 = 0.79.group 3 + 50 mL; r2 = 74.81%; r = .87; n = 28; group 1-group 3 +/- 1 SD = -506 +/- 374 mL. CONCLUSIONS: The results demonstrate that the blood volume estimate of the fiberoptic monitoring system (group 1) correlates closely with the total blood volume measurement using Evans blue (group 2) and indocyanine green (group 3). Trapped indicator in the packed red cell column after centrifugation of the blood samples may account for an overestimation of group 2 and group 3 of approximately 10% to 14%, but there still remains a proportional difference of 10% between group 1 vs. group 2 and vs. group 3. This difference is due to the longer mixing times of group 3 (16 mins) and group 2 (17 mins), during which they are distributed in slowly exchanging blood pools. It seems that the blood volume estimate of the fiberoptic monitoring system (group 1) represents the actively circulating blood volume and may be useful for bedside monitoring.

Comparison of ketamine and pentobarbital anesthesia with the conscious state in a porcine model of Pseudomonas aeruginosa septicemia.

Live Pseudomonas aeruginosa (2.5.10(9).kg-1.h-1) were administered to awake (Group A, n = 10) and anesthetized piglets, which were given intravenous ketamine (Group K, 10 mg.kg-1.h-1, n = 8) or pentobarbital (Group P, 15 mg.kg-1.h-1, n = 8). The anesthetized animals were mechanically ventilated. In addition, a pentobarbital group (Group CP, n = 6) and a ketamine control group (Group CK, n = 6) were studied. The mean survival time was 10.5 +/- 3.0 h in Group A, 10.6 +/- 2.8 h in Group K, and 1.8 +/- 1.3 h in Group P. In Group P the arterial pressure, the cardiac output and the systemic vascular resistance declined soon after start of the bacterial infusion, whereas the pulmonary artery pressure increased. The animals died of irreversible circulatory failure. In Group K pronounced pulmonary hypertension and lethal pulmonary edema developed. There was no circulatory failure in Group A, but the animals also died of marked pulmonary edema. Groups CP and CK exhibited stable hemodynamics for a period of 8 h. The results of this study suggest a deleterious effect of pentobarbital on hemodynamics and survival time, and a minor suppressive action of ketamine on the circulation in septicemia. Therefore, data obtained from septic shock studies applying pentobarbital have to be evaluated carefully. Investigation of the effects of gram-negative bacteria or endotoxin should be performed in unanesthetized or, if anesthesia is necessary, in ketamine-anesthetized animals.

Monitoring free flaps using laser-induced fluorescence of indocyanine green: a preliminary experience.

In a prospective, clinical study, the clinical utility of indocyanine green for intraoperative monitoring of free tissue transfer was evaluated. The study comprised 20 surgical patients undergoing elective microsurgical procedures. Indocyanine green angiography was performed intraoperatively, immediately after flap inset, and the operating team was blind to the fluoremetric findings. Thereafter, postoperative monitoring was done exclusively by clinical examination (color, temperature, time for recapillarization, and bleeding after puncture). Final outcome was compared with results of perioperative indocyanine (ICG)-imaging, and classified either as total flap loss, partial flap loss, or successful tissue transplantation. A total of 2 (10%) complications was recorded, and included one partial and one total flap loss. Both complications were detected by intraoperative ICG imaging. Another case of intraoperative subclinical arterial spasm at the place of microvascular anastomosis was revealed by dynamic ICG-videography. This flap did not develop postoperative complications. In conclusion, evaluation of perfusion by ICG imaging is feasible in all kinds of microsurgical flaps, irrespective of the type of tissue. Even though not meeting all the criteria of an ideal monitoring device, significant additional information can be obtained. In this study, cases with arterial spasm, venous congestion, and regional hypoperfusion were revealed by intraoperative ICG-videography. There was a strong correlation between intraoperative findings and clinical outcome.

Indications for combined high frequency ventilation in clinical use.

A retrospective study of 20 surgical intensive care unit patients is reported. They were ventilated with continuous positive pressure ventilation (CPPV) and then switched to combined high frequency ventilation (CHFV). To find why there were variable responses to CHFV, the data of 20 patients were retrospectively evaluated with respect to respiratory index (RI), compliance (C) and extravascular lung water (EVLW). The results suggest that the indication line for CHFV was a C value greater than 45 ml/cmH2O and an EVLW value greater than 15 ml/kg BW.

Intraoperative evaluation of skin-flap viability using laser-induced fluorescence of indocyanine green.

Laser-induced fluorescence of indocyanine green (ICG) is a new method for evaluating skin perfusion, which is superior to conventional fluorescein angiography. In a prospective clinical study ICG fluorescence video-angiography was used for the intraoperative evaluation of skin-flap perfusion. The results of ICG imaging were compared with clinical outcome 1 week postoperatively. Intraoperative ICG filling defects were always associated with delayed wound healing. In 50% of the patients, the regions of sloughing and epitheliolysis corresponded accurately to the regions of dye-filling deficits. All of the flaps without ICG filling defects healed primarily. These results suggest that ICG fluorescence is a sensitive tool for assessing nutritive blood flow in pedicled skin flaps with and without an axial vessel. Future clinical studies are required to establish critical threshold fluorescence indices that correlate with skin viability in the postoperative course.

Cortisol deficiency in metomidate anesthetized bacteremic pigs: results in circulatory failure--beneficial effect of cortisol substitution.

Etomidate and the closely related metomidate are known to inhibit cortisol synthesis. We studied the influence of metomidate on hemodynamic performance and survival time of bacteremic pigs. Thirty pigs, 30.2 +/- 0.8 kg, were anesthetized with intravenous metomidate (2.5 mg.kg-1.h-1) plus ketamine (3.0 mg.kg-1.h-1), and were then mechanically ventilated. The animals were randomly allocated to three groups of 10 pigs each. Group A received an infusion of live Pseudomonas aeruginosa bacteria (2.5.10(9).kg-1.h-1 organisms until death), Group B additionally received a bolus of 1 mg.kg-1 cortisol (followed by an infusion of 0.1 mg.kg-1.h-1) starting 1 h prior to the bacterial infusion, and Group C served as anesthesia control without receiving bacteria or cortisol. The experiments in Group C were terminated after 10 h. In Group A the cortisol level was severely suppressed from the very beginning. The animals died of circulatory failure after 4.3 +/- 0.4 h. In contrast, Group B exhibited fairly stable hemodynamics, but the animals died due to pulmonary edema after 11.1 +/- 1.3 h. Cortisol deficiency in metomidate anesthetized pigs facilitates the development of circulatory failure in the course of Pseudomonas bacteremia, which does not occur if cortisol is infused to reconstitute a physiological level. However, this cortisol substitution did not prevent the development of pulmonary edema caused by Pseudomonas aeruginosa. Possible mechanisms of the deleterious effect of cortisol deficiency and implications in regard to the clinical use of metomidate/etomidate are discussed.