Measurement of gastric mucosal carbon dioxide tension by saline and air tonometry

This study compares the balloon air tonometry method of measuring gastric mucosal CO₂ to standard saline tonometry. Also, this study investigates the effect of histamine-2 receptor blockade on the precision of tonometric measures of gastric mucosal Pco₂ (P_tco₂).

We obtained hourly measurements of P_tco₂ from two gastric tonometers inserted orally in 19 healthy volunteers. One tonometer measured P_tco₂ by the intermittent saline method, whereas the other measured P_tco₂ using a newer continuous air method. Subjects received intravenous 5% dextrose during the first 6 hours of the experiment followed by a continuous infusion of a solution of ranitidine in 5% dextrose for another 6 hours. The ranitidine infusion was titrated to maintain gastric fluid pH ≥ 4.

Comparison of air to saline tonometry yielded a bias of −1.3 mm Hg with a limit of agreement of 6.6 mm Hg under optimal conditions of optimal gastric fluid pH (gastric fluid pH ≥ 5.0). Measures of P_tco₂ were lower with ranitidine for either group, 45.3 ± 1.3 mm Hg versus 39.7 ± 0.5 mm Hg for saline (P < .01) and 45.9 ± 1.0 versus 41.3 ± 0.5 for air (P < .01). The mean Pco₂ gap (P_tco₂ - P_arterialco₂) at gastric fluid pH ≥ 5.0 was 1.4 mm Hg, with a standard deviation of 2.7 mm Hg. A span of three standard deviations yields a normal limit for Pco₂ gap of 9.5 mm Hg.

Measures of P_tco₂ with the air tonometer method are similar to those obtained with saline tonometry. The reliability of P_tco₂ measurements with either method improved with the use of ranitidine to maintain gastric fluid pH ≥5.     

Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs

: The lazaroids are a new class of potent free-radical scavengers. We tested whether U-74389G, a lazaroid, could attenuate some of the adverse cardiopulmonary effects of sepsis.

: Dogs were randomized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchange, they were then randomized to receive either 0.2 mg/kg endotoxin or a saline infusion. Measurements of hemodynamics and gas exchange were repeated. The study was concluded 70 minutes after endotoxin infusion and the lungs were then removed for histologic evaluation.

: In endotoxin-treated control animals, P0₂ decreased (278 ± 123 mm Hg to 67 ± 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% ± 1.1% to 28.2% ± 11.4%, P < .05) after endotoxin. Pretreatment with U-74389G attenuated the decrease in PO₂ (476 ± 61 mm Hg to 226 ± 143) and the increase in intrapulmonary shunt (12.6% ± 6.1% to 14.3% ± 6.8%) observed after endotoxin. The extent of lung injury and systemic hemodynamics were similar between control or U-74389G-treated dogs.

: A free-radical-scavenger can attenuate the gas exchange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics.     

Blood interleukin 10 levels parallel the severity of septic shock

The aim of this study was to investigate the relation between interleukin (IL) 10, tumor necrosis factor alpha (TNF), IL-1, and IL-6 levels in patients with septic shock and relate these cytokine levels to the development of organ failure.

In 11 patients with septic shock of recent onset, blood was sampled for determinations of TNF, IL-1, IL-6, and IL-10. The degree of organ failure was scored for four organ systems (respiratory, hepatic, renal, hematologic) in the first 48 hours of the study.

The APACHE II score was 21 ± 4. Three patients died. IL-10 levels were directly correlated with TNF levels (r = 0.73, P < .05) and IL-6 levels (r = 0.67, P < .05); and inversely correlated with total C3 (r = −0.73, P < .05) and CH50 (r = −0.68, P < .05). Both IL-10 and TNF levels were correlated to the organ failure score (r = 0.75 and r = 0.68, both P < .01). Six patients with high IL-10 levels (>60 pg/mL) had lower C3 (37 ± 11 v 62 ± 10 mg/dL) and CH50 (32 ± 7 v 68 ± 19%), and higher organ failure scores (5.7 ± 0.8 v 3.8 ± 1.3) than those with low IL-10 levels (all P < .05).

Although IL-10 has an inhibitory effect on the production of cytokines, it is released together with TNF and IL-6 in patients with septic shock. IL-10 blood levels are directly related to the severity of inflammation and the development of organ failure in septic shock.     

Flow triggering added to pressure support ventilation improves comfort and reduces work of breathing in mechanically ventilated patients

The purpose of this study was to measure the effect of flow triggering (FT), added to pressure support ventilation (PSV), during spontaneous breathing in intubated patients.

A prospective observational study was conducted at a Comprehensive Cancer Center, University Hospital. Fourteen consecutive critically ill, mechanically ventilated patients on PSV with positive end-expiratory pressure were studied. Flow triggering was added to PSV in spontaneously breathing ventilated patients.

Respiratory rate (f), minute ventilation (V), patient work of breathing (WOB_p), respiratory drive (P_0.1), rapid shallow breathing index (f/V_t), tidal volume (V_t) and a visual analog scale of breathing effort and comfort all improved. There was a large decrease in WOB_p, and P_0.1, when flow triggering was added to PSV (P < .001). There was a moderate decrease in f/V_t during the same procedure (P < .01). Twelve patients felt subjectively better with the intervention.

Flow triggering offers an excellent complement to PSV because it improves patient comfort and reduces the magnitude of the inspiratory effort as well as the delay time between inspiratory muscle contraction and gas flow. It augments gas exchange at no metabolic cost to the patient while reducing the work of breathing.     

Heat shock protein (HSP70) expression in septic patients

: This study investigates heat shock protein 70 (HSP₇₀) expression by peripheral blood mononuclear cells (PBMCs) of septic patients admitted to an intensive care unit and examines the possibility of a correlation between HSP₇₀ levels and plasma tumor necrosis factor alpha (TNF-) concentrations. Additionally, we evaluated whether the HSP₇₀ production could be regarded as a prognostic factor for the development of septic shock as well as for patient survival.

: Blood samples of 29 patients were taken 24 hours after the diagnosis of sepsis. HSP₇₀ expression and TNF- level were measured using indirect immunofluorescent analysis and a commercially available enzyme-linked immunosorbent assay method, respectively.

: PBMCs expressed significantly high levels of HSP₇₀ (11.9 ± 5.6 [sd]) compared with those of the healthy control group (3.2 ± 2.1 % positive cells). Such enhanced levels were correlated to plasma TNF- concentrations (r = .99, P < .01). This study failed to demonstrate a relationship between HSP₇₀ production and clinical outcome.

: These findings give further evidence that also in humans, heat shock response is activated during sepsis. The correlation observed between HSP₇₀ overproduction and TNF- plasma concentrations suggests that HSP₇₀ exerts a possible protective effect against TNF- cytotoxicity. Such hypothesis has not been confirmed by our clinical data.     

Nitric oxide metabolism in canine sepsis: relation to regional blood flow

To investigate the role of nitric oxide (NO) in early endotoxemia on the systemic and regional blood flow by measuring the plasma nitrite/nitrate (NOx) and blood nitrosyl-hemoglobin (NO-Hb) levels.

This was a prospective, controlled, experimental study conducted in an animal research laboratory on 15 male mongrel dogs. Escherichia coli endotoxin (1 mg/kg) was injected intravenously.

Hepatic, renal, and iliac blood flow and cardiac output (CO) were measured before and 15, 30, 45, 90 and 180 minutes after injection of Escherichia coli endotoxin (1 mg/kg) (n = 6). NOx efflux from the organs was calculated by measuring plasma NOx levels. The arterial blood levels of NO-Hb were also measured (n = 4). As control studies, blood samples from dogs (n = 5) without exposure to endotoxin were assayed at 180 minutes for NOx and NO-Hb. Following endotoxin injection, mean arterial pressure decreased and reached its lowest value at 90 minutes (baseline vs. 90 minutes: 119.1 ± 5.8 vs. 82.5 ± 16.7 mm Hg, P < .0001). Hepatic artery bloodflow increased significantly (baseline vs. 180 minutes: 23.6 ± 12.0 vs. 170.0 ± 68.4 mL/min, P < .0001). There were no significant changes in plasma levels of NOx, uptake or release of NOx across the measured vascular beds, NO-Hb levels at anytime point. In the portal system, the portal vein flow correlated with NOx release (R = 0.69, P < .0001).

In the early phase of endotoxemia in the dog, the significant reduction in systemic vascular resistance and hepatic arterial resistance are not associated with any measurable NOx release in the systemic circulation or the liver.     

The relationship between the arteriovenous carbon dioxide gradient and cardiac index

It has been reported that under normal conditions, mixed venous blood gases have approximated arterial samples; however, during cardiac arrest or severe cardiogenic shock, marked differences between arterial and venous blood gases have been noted. To further assess the relationships between arterial and mixed venous blood gases and cardiac index, a study population was chosen consisting of patients with less severe states of cardiac impairment. The differences between arterial and mixed venous P ₂S and pHs were compared with cardiac indexes (CI) of 44 patients in an intensive care unit with arterial lines and Swan-Ganz catheters in place. Twenty-six patients with normal Cis (2.6 to 4.1 L/min/m²) had a mean difference in mixed venous-arterial P ₂ (ΔP ₂) of 4.88± 0.40 mm Hg. In patients with low Cis (< 2.6), the ΔP ₂ was 7.44 ± 0.63 mm Hg (P = .001). The difference of mixed venous and arterial pH (ΔpH) was 0.027 ± 0.004 pH units for patients with normal Cis and 0.04 ± 0.003 pH units for those with low Cis (P < .002). When the Cls of all patients were plotted against the ΔP ₂s, there was an inverse linear relationship wherein ΔP ₂ increased as Cl decreased (r = −.47, P = .0011). There is an inverse relationship between ΔP ₂ and Cl that has not been previously described. An elevated ΔP ₂ may be a marker of a low cardiac index.     

Reversal of muscle fatigue in intact rabbits by intravenous potassium chloride

Skeletal muscle fatigue has been associated with potassium efflux from the myocytes, resulting in endogenous increases in blood potassium concentration ([K⁺]). Conversely, exogenous increases in extracellular [K⁺] potentiates contraction in isolated muscle preparations. The mechanisms responsible for these contradictory effects of [K⁺] on skeletal muscle function are unknown. Moreover, little is known about the effect of exogenous increases in [K⁺] on force generation by intact animals, given potassium's deleterious effect on cardiac function.

We compared the response to exogenous increases in blood [K⁺] in rabbits given an infusion of potassium chloride (KCl) intravenously (IV) (0.2 mol/L; KCl group; N = 7) to a group given 0.9% sodium chloride (NaCl) (control; N = 7). The rabbits underwent low-frequency, isometric twitch stimulation of the left hindlimb (square wave pulses 100 microseconds, 40V, 0.25 Hz) throughout the experiment. Both groups received 0.9% NaCl (25 mL/h) during the first hour of twitch stimulation and experienced similar decreases in hindlimb forces to 70% of initial force. A continuous infusion of KCl or of saline (60 mL/h) was started, and hindlimb stimulation continued for 2 hours.

There were no changes in [K⁺] in the control group, and twitch forces progressively declined during the next 2 hours (369 ± 47 g to 279 ± 34 g, P < .01). Arterial [K⁺] increased in the KCI group from 2.6 ± 0.1 to 10.1 ± 0.5 mmol/L (P <.01), and hindlimb twitch forces almost doubled (418 ± 49 g to 756 ± 55 g, P < .01). Force frequency curves showed improved contractility in the KCI group at stimulation frequencies below 30 Hz.

Exogenous increases in blood [K⁺] potentiate skeletal muscle contraction in intact animals and reverse low-frequency twitch fatigue. A possible mechanism may be the maintenance of intracellular [K⁺] by hindering K⁺ efflux from skeletal muscle cells.     

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

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.

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 thermodilution, and ITBV was measured by double-indicator dilution.

CI was correlated to CVP with r² = .42 (P ≤ .01), to PAOP with r² = .43 (P ≤ 5.01), to RVEDV index with r² = .21 (P ≤ .01), and to ITBV with r² = .78 (P ≤ .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 × min⁻¹) and CI by 30% in normovolemia and hypovolemia, while ITBV remained basically unchanged.

Under the experimental conditions choosen 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.     

Influence of preoperative mechanical bone quality and bone mineral density on aseptic loosening of total hip arthroplasty after seven years

Objective. To test mechanical bone quality and bone mineral density of the femoral head at the day of implantation as indicators for femoral prosthesis loosening.

Methods. Mechanical bone quality of a femoral head slice was assessed by destructive compression testing combined with bone mineral density measurements using peripheral quantitative computed tomography. Fourteen patients with walking pains were attainable for a radiographical follow-up mean 7.1 years after implantation.

Results. Radiolucent lines along the stem were evident in 11 of 14 femurs, most of them seen in Gruen zones 7, 6, 1, 3, 14, and showed strong correlations to preoperative bone strength (r=−0.80; P<0.001) and axial stiffness (r=−0.75; P=0.002), yet not to bone mineral density (r=−0.67; P=0.009). Slight varus deviations <3° were noted in six femurs. Preoperative strength was reduced in this femurs to 54% (P=0.006), and stiffness to 61% (P=0.038), while bone mineral density did not differ significantly.

Conclusions. Femoral prosthesis loosening after seven years can be predicted by mechanical bone quality of the femoral head at the time of implantation. Bone mineral density measurements may also indicate future stem loosening but have to interpreted carefully, keeping in mind a poorer predictive value.

Relevance Indications and choice of type of hip arthroplasty should be balanced in osteoporotic bones in particular. While preoperative bone mineral density measurement allows the prediction of mechanical bone quality, its relevance in predicting failure in arthroplasty treatment remains unclear.     

Ischemia/reperfusion injury to the ileum does not account for the ileal Vo2-Do2 alterations induced by endotoxin

Endotoxin (lipopolysaccharide [LPS])-induced systemic organ injury leads to disruption of normal systemic organ metabolic processes, which are manifest clinically by signs of accelerated anaerobic metabolism (eg, tissue acidosis and hyperlactatemia) and altered Vo₂-Do₂ relationships. The association of increased anaerobic metabolism with Vo₂-Do₂ alterations has led to the notion that ischemia/reperfusion (I/R) injury may be a prerequisite for the development of Vo₂-Do₂ alterations during endotoxemia. However, in contrast to sepsis, in which oxygen consumption is often increased, oxygen consumption is severely decreased after I/R injury. Based on these observations, we hypothesized that I/R injury would result in systemic organ Vo₂-Do₂ alterations, which are distinct from those that occur in sepsis.

We used the in situ autoperfused feline ileal preparation to simultaneously examine microvascular permeability, reflected as the ileal lymph to plasma protein concentration ratio (C_L/C _P), and ileal Vo₂-Do₂ relationships after either intravenous LPS (2.0 mg/kg; N = 5) or I/R injury (n = 5), and in matching controls (n = 5).

As expected, all LPS-treated and I/R-injured animals were found to have extensive ileal histological damage and marked increases in the C_L/C_P compared with controls (0.315 ± 0.009 and 0.329 ± 0.034, respectively, v 0.097 ± 0.009; P < .001, both comparisons). In addition, the critical Do₂ (Do₂c) was elevated, and the critical oxygen extraction was decreased in both the I/R and LPS groups relative to controls. However, as initially hypothesized, the Vo₂ at the critical Do₂ was markedly decreased in the I/R group compared with that of the LPS group.

These data indicate that I/R injury is insufficient to account for the systemic organ Vo₂-Do₂ alterations that occur with LPS injury.     

Anti-CD18 antibodies improve cardiac function following cardiopulmonary bypass in dogs

Cardiopulmonary bypass is associated with activation of neutrophils, which may adhere to vascular endothelium causing lung, heart, and brain injury. We tested whether blocking neutrophil adherence would improve organ function following cardiopulmonary bypass in dogs.

Ulbar|Materials and Methods: All dogs received a standard anesthetic, and then one group (n = 6) received 2 hours of cardiopulmonary bypass followed by 4 hours of observation. A second group (n = 6) received a monoclonal antibody (6 mg/kg) to CD18, a neutrophil adherence factor, immediately before cardiopulmonary bypass. A third group (n = 6) did not receive cardiopulmonary bypass or antibody.

Using flow cytometry we found that the antibody bound essentially all neutrophil CD18 sites. All three groups had similar gas exchange and hemodynamics. Lung and heart histology results were similar between groups. By echocardiography, five animals receiving cardiopulmonary bypass alone showed regional wall abnormalities, whereas only one receiving antibody showed wall motion abnormality (P < .05). Following cardiopulmonary bypass, intracellular myocardial pH was higher (P < .05) in the antibody-treated group compared with the group that had cardiopulmonary bypass alone (7.23 ± 0.05 v 7.07 ± 0.07 respectively).

Monoclonal antibodies to CD18 can prevent the deterioration in cardiac function routinely observed following cardiopulmonary bypass.     

Effects of N-acetylcysteine in endotoxic shock

: The release of oxygen-free radicals has been implicated in both peripheral vascular and myocardial alterations of septic shock. N-Acetylcysteine (N-AC), a substrate for the production of glutathione, has potent antioxidant effects. As a nitrosothiol, it may also improve capillary blood flow. We studied the effects of N-AC in a dog model of endotoxic shock.

: Ten pentobarbital-anesthetized, mechanically ventilated dogs were randomly assigned to receive either N-AC (150 mg/ kg loading dose in 1 hour, followed by 20 mg/kg · h maintenance dose) or D5W. After the loading dose, each dog received 3 mg/kg Escherichia coli endotoxin intravenously. After 30 minutes, saline infusion was started to restore and maintain baseline filling pressures.

: The loading dose of N-AC increased Do₂ significantly (from 661 ± 54 to 914 ± 190 mL/min, P < .05), but Vo₂ remained stable. After the administration of endotoxin, fluid challenge restored cardiac output to baseline, in both groups. Hemoglobin and, thus, Do₂ were slightly lower in the N-AC-treated dogs, but Vo₂ was similar in both groups. At the end of the study, O₂ER was significantly higher in the N-AC-treated dogs than in the control dogs. Blood lactate levels fell more rapidly in the N-AC dogs than in the control dogs. Blood lactate levels returned to normal in the N-AC dogs but not in the control dogs. Tumor necrosis factor (TNF) also decreased significantly in the N-AC dogs but remained elevated in the control dogs.

: These data indicate that N-AC administration in endotoxic shock is well tolerated, may increase oxygen availability to the tissues, and is associated with an attenuation of TNF release.     

Circuit factors in the high cardiac output of sepsis

The increase of cardiac output (CO) in sepsis must be matched by an increase in venous return. Our goal was to determine which of the determinants of venous return are responsible in volume-loaded and nonvolume-loaded pigs with endotoxemia. The determinants include stressed volume, venous compliance (C_v), venous resistance (RVR) and right atrial pressure (Pra). We also tested the effect of the nitric oxide (NO) synthase inhibitor, N^ω-nitro- -arginine-methyl ester (L-NAME) after the hemodynamics with endotoxin stabilized.

Pigs were anesthetized and mechanically ventilated. We measured CO by thermodilution, mean circulatory filling pressure (MCFP) by inflating a balloon in the right atrium, blood volume by dye dilution, and C_v by rapid blood infusions. RVR was calculated from MCFP - Pra/CO). After baseline measurements, we infused 10 μg/(kg x h⁻¹) of Escherichia coli endotoxin. Eight animals also received 30 mL × kg⁻¹ of dextran over the 2 hours (volume treated), and seven did not (no volume). After 2 hours we injected 25 mg × kg⁻¹ of the NO synthase inhibitor, L-NAME, and repeated the measurements.

In volume-treated animals, CO increased from 3.9 ± 0.7 to 5.4 ± 0.8 L x min⁻¹ (P < .05), and blood pressure (BP) fell from 118 ± 9 to 76 ± 12 mmHg. MCFP rose, and there was no change in RVR or C_v, whereas capacitance increased (ie, right shift of pressure-volume curve). Cardiac function (ie, Starling curve) did not change. In no-volume animals, CO fell from 4.47 ± 0.64 to 2.50 ± 0.86 L × min⁻¹, BP from 114 ± 10 to 9 13 mmHg and MCFP fell. Systemic vascular resistance did not change. Cardiac function was markedly depressed, and the heart rate increased from 143 ± 13 to 203 ± 30 beats x min⁻¹. L-NAME restored BP in both groups but also increased RVR and depressed cardiac function.

Changes in vascular tone during endotoxemia are dependent on volume status. The increased cardiac output in volume-treated septic animals occurred because of an increase in stressed volume due to the volume given in combination with a dilated vasculature. L-NAME restored arterial tone but decreased CO because of a rise in RVR and decrease in cardiac function.     

Randomized evaluation of controlled-release codeine and placebo in chronic cancer pain

Codeine is widely used in combination with acetaminophen and aspirin for the management of mild to moderate pain. However, there are few controlled clinical trials of single-entity codeine in chronic cancer pain. The purpose of this study was to evaluate the clinical efficacy and safety of controlled-release codeine given every 12 hr in patients with cancer pain. Thirty-five patients with chronic cancer pain were randomized in a double-blind crossover study to controlled-release (CR) codeine or placebo, for 7 days each. Pain intensity was assessed at 0800 hr and 2000 hr using a visual analogue scale (VAS) and a five-point categorical scale, and the use of “rescue” acetaminophen-plus-codeine (300 mg/30 mg every 4 hr as needed) was recorded. Thirty patients completed the study (17 male, 13 female; mean age, 64.4 ± 9.8 years) with a mean daily CR codeine dose of 277 ± 77 mg (range, 200–400 mg). CR codeine treatment resulted in significantly lower overall VAS pain intensity scores (22 ± 0.8 mm versus 36 ± 20 mm, P = 0.0001), categorical pain intensity scores (1.2 ± 0.8 versus 1.8 ± 0.8, P = 0.0001), and pain scores when assessed by day of treatment and by time of day. Daily “rescue” analgesic consumption was significantly lower on CR codeine, compared to placebo treatment (2.2 ± 2.3 versus 4.6 ± 2.8 tablets per day, P = 0.0001). Both patients and investigators preferred CR codeine to placebo (80% versus 3%, P = 0.0014 and 73% versus 7%, P = 0.0160, respectively). These data indicate that CR codeine, given every 12 hr results in significant reductions in pain intensity and the use of “rescue” acetaminophen-plus-codeine in patients with cancer pain. CR codeine provides the benefits of a flexible single entity codeine formulation and the convenience of 12-hr duration of action, which allows patients uninterrupted sleep and improved compliance.     

The effect of auto-positive end-expiratory pressure on the arterial-end-tidal carbon dioxide pressure gradient and expired carbon dioxide slope in critically ill patients during total ventilatory support

To examine the effect of auto-positive end-expiratory pressure (autoPEEP) on the estimation of arterial carbon dioxide pressure (PaCO₂) from end-tidal carbon dioxide pressure (PetCO₂) during changes in minute ventilation (MV), we studied 24 consecutive sedated and paralyzed patients under controlled mechanical ventilation for acute respiratory failure. The patients were grouped according to whether they had autoPEEP: group I (n = 11) comprised non-autoPEEP patients and group II (n = 13) comprised autoPEEP patients. Patients were randomly ventilated at three different levels of MV: normal MV (basal tidal volume), high MV (tidal volume 2.5 mL/kg above basal), and low MV (tidal volume 2.5 mL/ kg below basal). Respiratory rate and inspiration to expiration ratio were kept constant during the study. In each condition, we measured arterial blood gases, expiratory capnograms, airway pressure, and autoPEEP. We determined PaCO₂-PetCO₂ gradient, predicted PaCo₂ (Pa'CO₂) [Pa'CO₂ = PetCO₂ for each condition + (PaCO₂ PetCO₂ gradient at normal MV)], and expired CO₂ slope. The PaCO₂-PetCO₂ gradient only remained stable in group I (mean values for low, normal, and high MV were 3.3, 3.3, and 3.5 mm Hg, respectively), while group II showed a significant difference during low MV (12.2 mm Hg) when compared with normal MV (8.4 mm Hg; P < .01) and high MV (8.9 mm Hg; P < .05). PaCO₂ and PetCO₂ showed significant correlations in both groups (r = .92 in group I and .79 in group II). However, Pa'CO₂ could only be safely estimated in patients without autoPEEP when the difference between PaCO₂ and Pa'CO₂, ranged between 1.6 and −1.9 mm Hg. Slopes of expired CO₂ greater than 3 mm Hg/s identified patients with autoPEEP of 89% sensitivity, 93% specificity, 94% positive predictive power, and 95% accuracy. A significant correlation was found between autoPEEP and expired CO₂ slope (r = .70; P < .001), between autoPEEP and PaCO₂-PetCO₂ gradient (r = .46; P < .001), and between CO₂ expired slope and PaCO₂ PetCO₂ gradient (r = .74; P < .001). These results indicate that in patients with acute respiratory failure under controlled mechanical ventilation, the presence of autoPEEP is associated with inaccuracy in the calculation of predicted PacoZ from PetcoZ after changes in MV at fixed respiratory rates.     

Human aortic elastin from normal individuals and atherosclerotic patients: lipid and cation contents; susceptibility to elastolysis

Aortic elastins, isolated from 30 humans of different ages, were purified by alkaline extraction, and separated into two groups depending on the presence of atherosclerotic plaques and calcification (grades 0 and 1).

It was confirmed that the severity of atherosclerosis increases significantly with age (P < 0.001) and elastin content decreases with atherosclerosis (P < 0.001). The hydrolysis of the aortic elastins using pancreatic porcine elastase (PPE) was studied. It was observed that increased elastolytic activities are connected with severity of atherosclerosis (P < 0.001) and both V_m and K_m apparent kinetic parameters are affected (P < 0.001). Correlation tests have shown that enzymatic hydrolysis is significantly modified by cholesterol (P < 0.05), calcium (P < 0.001) and magnesium concentrations (P < 0.01) but only cholesterol changes significantly V_m and K_m parameters.     

Advantages of dextran 70 over ringer acetate solution in shock treatment and in prevention of adult respiratory distress syndrome. A randomized study in man after traumatic-haemorrhagic shock

Twenty-three patients aged 20–58 years in a serious state of shock and suffering from major pelvic and femoral fractures sustained in traffic accidents were studied. As initial fluid management, either dextran 70 (1000–1500 ml) together with Ringer's acetate solution (2000–3000 ml), or Ringer's acetate alone (5000–8000 ml), was administered on a random basis. Thus, 12 patients received dextran and 11 patients crystalloid treatment to counteract shock. Both groups were given whole blood. The resuscitation time-i.e. the interval from the start of fluid therapy until a stable circulatory condition was achieved-was significantly shorter (P < 0.001) in the dextran group (108 ± 18 min; mean ± S.D.) than in the Ringer group (170 ± 43 min). During the post-resuscitative observation period of 6 days the dextran patients were given 500 ml of dextran daily, while the Ringer group did not receive any colloidal solution. To maintain a stable circulation and a urinary output above 50 ml/h the Ringer patients required significantly more (P < 0.001) crystalloid solution (910 ± 300 ml) daily than the dextran patients (460 ± 400 ml).

The frequency of adult respiratory distress syndrome (ARDS) was significantly lower (P < 0.05) in the dextran group (0 of 12) than in the Ringer group (4 of 11). Thus, in the initial treatment of traumatic-haemorrhagic shock and in the post-resuscitative period dextran 70 would seem of advantage over Ringer's acetate both in shortening the shock period and in reducing the frequency of adult respiratory distress syndrome.     

Value of elementary, combined, and modeled hemodynamic variables

: It has been well recognized that the usefulness of the clinical examination and simple hemodynamic variables in the critically ill is limited. Modelization for hemodynamic analysis may improve the diagnostic performance by a systematic and multivariate analysis. This requires a rigorous formalization that may otherwise expand the usefulness of hemodynamic data, both as predictors and as therapeutic targets. Our study was designed to test the value of a model for assessing the pathophysiology of circulatory disorders and for establishing the diagnosis.

: We tested all available variables using survival as the end point. A population of 223 patients (652 measurements) with compromised circulatory status was studied. We evaluated traditional variables: (1) morphological and physical data, (2) elementary right heart catheterization data, and (3) usually calculated variables, versus (4) new modeled variables. These new modeled variables were derived from a previously validated computer program for hemodynamic evaluation. They expressed differences between observed hemodynamic performance and estimated needs.

: Among traditional variables, major prognostic factors were: (1) in all patients, lactate level elevation, physical signs of hypoperfusion, and a decreased systemic arterial pressure; (2) in septic patients, a high Pao₂/Sao₂ ratio; (3) in nonseptic patients, low left ventricle work indices. In all cases, modeled hemodynamic variables assessing performance-needs adequacy enhanced the prognostic value of hemodynamic monitoring.

: Compared with traditional variables, modeled variables were found of greater interest to quantify pathophysiology of shock. These results enabled us to validate the initial step of the hemodynamic reasoning formalization and to develop “new” diagnostic criteria that more closely fit the interrelationship between pathophysiology, diagnosis, and prognosis.     

Increased cardiac output increases lung water in canine permeability pulmonary edema

We investigated the effects of increased cardiac output (CO) on oleic acid pulmonary edema in 14 open-chest, anesthetized, mechanically ventilated dogs. Pulmonary artery wedge pressure (Pawp) was adjusted to approximately 9 mm Hg via a left atrial balloon and CO to 1.7 L · m⁻¹ via systemic arteriovenous fistulas (AVF); five minutes after oleic acid (0.08 mL · kg⁻¹), dogs were randomly divided into two groups, high CO and low CO. In the high CO group, CO was increased by opening the AVFs. Pawp was maintained at 9 mm Hg for four hours in all dogs. The average CO time in the high CO group was 3.9 L · min⁻¹ and 1.3 L · min⁻¹ in the low CO group (P < .01). Lung water accumulation was significantly increased in the high CO group with a wet weight/ body weight ratio of 29 g ò kg⁻¹v 21 g · kg ⁻¹ in the low CO group (P < .004). With time, mean pulmonary artery pressure increased significantly (P < .05) in both groups, but was not different between groups at any time. While pulmonary vascular resistance remained constant in the high CO group, it increased markedly (P < .05) in the low CO group, possibly due to a decrease in pulmonary vascular surface area. The increase in lung water accumulation in the high CO group is probably due to prevention of pulmonary vascular derecruitment and therefore a greater perfused pulmonary vascular surface area.