Prostaglandin E1 increases oxygen extraction capabilities in experimental sepsis.

By its microvascular and anti-inflammatory actions, prostaglandin E1 (PGE1) has been suggested both in animal models and in humans to have a therapeutic value in sepsis. To investigate whether PGE1 could improve the oxygen extraction capabilities in severe sepsis, our study focused on the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during an acute reduction in blood flow induced by cardiac tamponade in endotoxic dogs. Thirty anesthetized, ventilated dogs were divided into three groups. A first group (N = 10) served as a control receiving 20 ml/kg/hr of saline intravenously. A second group (N = 10) received PGE1 at 100 ng/kg/min along with the same saline infusion. A third group (N = 10) received the same dose of PGE1 with only 1 ml/kg/hr of saline. Thirty minutes after the initiation of this therapy, Escherichia coli endotoxin (2 mg/kg) was injected in each dog. In each group, the administration of PGE1, fluids, or both was continued throughout the study. Tamponade was then induced by repeated bolus injections of warm saline into the pericardial space. Steady-state measurements of VO2 (derived from the expired gases) and DO2 (the product of cardiac index and oxygen content) were obtained sequentially after each saline injection. The administration of PGE1 + fluids resulted in significant increases in stroke volume, cardiac index, and DO2 and reductions in systemic and pulmonary vascular resistance. Stroke volume and cardiac index were lower in the PGE1 alone than in the PGE1 + fluids group. The VO2 levels at critical DO2 (DO2crit) were identical. However, DO2crit, which was 12.2 +/- 2.8 ml/kg/min in the control group, was significantly decreased to 9.8 +/- 2.0 ml/kg/min in the PGE1 + fluids and to 9.3 +/- 2.7 ml/kg/min in the PGE1 alone group (both P < 0.05). Critical oxygen extraction ratio (O2ERcrit) which was 47 +/- 14% in the control group, was increased to 63 +/- 16% in the PGE1 + fluids group and to 61 +/- 17% in the PGE1 alone group (both P < 0.05). To investigate whether PGE1 also improves oxygen extraction capabilities in the absence of endotoxin, a second series of experiments was performed in 14 dogs, receiving saline alone (Control, N = 7) or plus PGE1 at 100 ng/kg/min (PGE1, N = 7). DO2crit was 10.7 +/- 2.9 ml/kg/min in the PGE1 group vs 10.1 +/- 1.8 ml/kg/min in the control group (NS). O2ERcrit tended to be higher in the PGE1 group than that in the control group (68 +/- 13% vs 60 +/- 15%, P = 0.054).(ABSTRACT TRUNCATED AT 400 WORDS)

Pentoxifylline improves the tissue oxygen extraction capabilities during endotoxic shock.

Pentoxifylline (PTX), a xanthine derivative used in the treatment of circulatory insufficiency, has been found to have protective effects in different models of sepsis. We hypothesized that this drug might improve the cellular oxygen availability following endotoxin challenge by increasing oxygen delivery (DO2) and/or tissue oxygen extraction. The oxygen extraction capabilities were studied during a reduction in blood flow induced by cardiac tamponade. Fourteen anesthetized, ventilated, and paralyzed dogs, received intravenous 2 mg/kg of Escherichia coli endotoxin followed by a continuous infusion of 20 ml/kg.h of saline. 30 min later tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Seven dogs were pretreated with PTX as an intravenous bolus of 20 mg/kg, followed by a continuous infusion at 20 mg/kg.h, and the other seven dogs served as a control group. PTX largely attenuated the systemic and pulmonary vasoconstriction observed in the control group and resulted in significant increases in cardiac index, DO2 and oxygen consumption (VO2). PTX also improved ventilation/perfusion matching in the lungs as indicated by a higher PaO2 and PvO2 and a lower venous admixture than in the untreated group during cardiac tamponade (both p < .05). In addition, the critical DO2 (DO2 crit) was lower and the critical oxygen extraction ratio was higher in the PTX treated than in the control group (9.1 +/- 1.8 vs. 11.6 +/- 2.4 ml/kg.min, and 70.6 +/- 14.0 vs. 49.3 +/- 14.6%, both p < .05). The VO2/DO2 dependency slope was also steeper in the PTX-treated than in the control group (.80 +/- .28 vs. .43 +/- .19, p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Protective effects of N-acetyl-L-cysteine in endotoxemia.

Because oxygen free radicals have been implicated in the endothelial cell damage and in the myocardial depression occurring during severe sepsis, we investigated whether N-acetyl-L-cysteine (NAC) could influence the oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. Sixteen anesthetized, saline-infused, and ventilated dogs received Escherichia coli endotoxin (2 mg/kg) 30 min before tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Thirty minutes before endotoxin administration, nine dogs received NAC (150 mg/kg, followed by a 20 mg.kg-1.h-1 infusion); the other seven dogs served as a control group. The NAC group maintained higher cardiac index, oxygen delivery (DO2), and left ventricular stroke work index, but lower systemic and pulmonary vascular resistance, than the control group. The oxygen uptake (VO2) levels at critical DO2 (DO2crit) were identical in the two groups. However, DO2crit was significantly lower in the NAC than in the control group (8.1 +/- 1.7 vs. 10.8 +/- 1.8 ml.kg-1.min-1, P < 0.01). Critical oxygen extraction ratio and the slope of the VO2-to-DO2-dependent line were higher in the NAC than in the control group (72 +/- 14 vs. 53 +/- 15% and 0.80 vs. 0.56, respectively; both P < 0.05). The peak lactate and the maximal tumor necrosis factor (TNF) levels were lower in the NAC than in the control group (5.2 +/- 0.4 vs. 7.6 +/- 0.4 mM, and 0.14 +/- 0.03 vs. 1.21 +/- 0.58 ng/ml, respectively; both P < 0.01). NAC significantly increased glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic oxygen extraction can be improved during repeated episodes of cardiac tamponade.

We used a tamponade model to study the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during successive, reversible decreases in blood flow. In 7 pentobarbital-anesthetized and mechanically ventilated dogs, a catheter was introduced via a left thoracotomy into the pericardium to inject and to withdraw saline. Each experiment consisted of three steps. First, cardiac output was reduced by successive pericardial fluid injections until 4 to 6 data points were obtained in the dependent region of the VO2/DO2 plot (step 1). Second, cardiac output was restored by progressive withdrawal of pericardial fluid (step 2). Third, cardiac output was lowered again by reinjection of fluid into the pericardium until death (step 3). Expired gases were collected for determination of VO2. In each animal, critical DO2 (DO2crit), below which VO2 became DO2 dependent, was determined from a plot of VO2 versus DO2. When releasing tamponade, VO2 was restored to baseline. For the 3 steps, DO2crit were 10.5 +/- 2.2 mL/kg/min in step 1, 9.8 +/- 1.8 mL/kg/min in step 2, and 8.3 +/- 1.9 mL/kg/min in step 3 (P < .01 v step 1; P < .05 v step 2, respectively). There was no significant difference in VO2 at DO2crit for the three steps. Hence, critical oxygen extraction ratio (ERO2crit) increased from 60% +/- 12% in step 1 to 64% +/- 11% in step 2 (not significant) and to 73% +/- 12% in step 3 (P < .01). The VO2/DO2 dependency slope was also steeper in step 3 than in step 1 (0.77 +/- 0.31 v 0.54 +/- 0.20, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal pattern of breathing during active and quiet sleep after maternal administration of meperidine.

The aim of this study was to reappraise the effects of maternal meperidine administration on breathing pattern during the first hours of life taking into account the state of alertness. Because breathing instability is more pronounced during active sleep, we hypothesized that meperidine administration might create a greater risk for respiratory instability during active sleep, the prominent sleep state in newborns. We studied eight full-term, healthy newborns whose mothers had received a continuous i.v. infusion of meperidine (81 +/- 9 mg) that was terminated 5.5 +/- 2.1 h before delivery. These infants were compared with a control group of eight full-term newborns whose mothers did not receive any opioids. In both groups, all babies were delivered vaginally after a normal labor and had Apgar scores of 9 or 10 at 1 and 5 min. Neonatal gastric secretion and maternal venous and umbilical venous blood were sampled at delivery for determination of meperidine concentration. From 60 to 300 min after delivery, behavioral sleep states and thoracic and abdominal movement as well as transcutaneous arterial oxygen saturation (SaO2) were monitored continuously. The number of apneic spells lasting more than 3 s during 100 min of recording and the percentage of time with SaO2 below 90% in each sleep state were recorded. During quiet sleep, all respiratory variables were similar in both groups. During active sleep, there were significantly more apneic episodes (37.1 +/- 25.1 versus 11.2 +/- 13.9) and a higher percentage of time with SaO2 less than 90% (14.3 +/- 16.7% versus 1.3 +/- 1.5%) in the meperidine group than in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal muscle activity during CO2 rebreathing in sleeping neonates.

Comparison of the abdominal muscle response to CO2 rebreathing in rapid-eye-movement (REM) and non-REM (NREM) sleep was performed in healthy premature infants near full term. Eight subjects were studied at a postconceptional age of 40 +/- 1.6 (SD) wk (range 38-43 wk) during spontaneous sleep. Sleep stages were defined on the basis of electrophysiological and behavioral criteria, and diaphragmatic and abdominal muscle electromyographic activity was recorded by cutaneous electrodes. The responses to CO2 were measured by a modified Read rebreathing technique. The minute ventilation and diaphragmatic and abdominal muscle electromyographic activities were calculated and plotted against end-tidal CO2 partial pressure. Both the ventilatory and diaphragmatic muscle responses to CO2 decreased from NREM to REM sleep (P less than 0.05). Abdominal muscles were forcefully recruited in response to CO2 rebreathing during NREM sleep. In REM sleep, abdominal muscle response to CO2 was virtually absent or decreased compared with NREM sleep (P less than 0.05). We conclude that 1) the abdominal muscles are recruited during NREM sleep in response to CO2 rebreathing in healthy premature infants near full term and 2) the abdominal muscle recruitment is inhibited during REM sleep compared with NREM sleep, and this REM sleep-related inhibition probably contributes to the decrease in the ventilatory response to CO2 rebreathing in REM sleep.

Neonatal patterns of breathing after cesarean section with or without epidural fentanyl.

The pattern of breathing and lung mechanics were evaluated during the first 7 h of life in full-term healthy newborns delivered by cesarean section with bupivacaine epidural anesthesia, without (group 1) or with the addition of 100 micrograms of fentanyl (group 2). Respiration and oxyhemoglobin saturation (SpO2) were measured with calibrated inductive plethysmography and pulse oximetry, respectively, and recorded from 60-420 min following birth. Compliance of respiratory system (CRS) was measured using a multiple occlusion technique at 60 and 420 min. Pattern of breathing was compared during period I (60-240 min) and II (240-420 min) with the following results: 1) the number of apnea spells was similar in both groups during both periods; 2) in both groups, from period I to period II a significant decrease in apnea duration was observed (7.6 +/- 0.7 s-4.1 +/- 0.5 s in group 1 and 6.7 +/- 1.2 s-5.1 +/- 1.0 s in group 2, respectively (P less than 0.05); 3) respiratory rate (RR) and minute ventilation (VE) were similar in both groups during both study periods; and 4) both RR and VE significantly decreased in the two groups from period I to period II (i.e., 59 +/- 5-46 +/- 2 breath per min-1 and 313 +/- 60-248 +/- 24 ml.kg-1.min-1 in group 1, and 60 +/- 2-51 +/- 1 breath.min-1 and 318 +/- 12-290 +/- 12 ml.kg-1.min-1 in group 2, respectively; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Passive compliance of the total respiratory system in newborn infants born by cesarean section]. / Compliance passive du système respiratoire total chez des nouveau-nés nés par césarienne.

The compliance of the total respiratory system (CRS) was measured by the occlusion technique: a) at H1-H2, H6-H7 and D3-D4 in 8 full-term newborns after cesarean section; b) at H1-H2 and H6-H7 in 6 full-term newborns delivered vaginally and at D3-D4 in 10 full-term newborns delivered vaginally. At H1-H2 respiratory frequency measured by inductive plethysmography was not significantly different between newborns after cesarean section (60 +/- 6 c/min) and newborns delivered vaginally (53 +/- 16 c/min). CRS normalized for body weight was not significantly different between newborns after cesarean section and those delivered vaginally at H1-H2 (0.6 +/- 0.1 vs 0.7 +/- 0.1 ml/cmH2O/kg) and at H6-H7 (0.7 +/- 0.1 vs 0.8 +/- 0.3 ml/cmH2O/kg). At D3-D4, CRS was significantly greater than at H6-H7 in newborns after cesarean section (1.1 +/- 0.2 ml/cmH2O/kg, p less than 0.001) and in newborns delivered vaginally (1 +/- 0.1 ml/cmH2O/kg, p less than 0.02). We conclude that in newborns after cesarean section without tachypnea, the evolution in CRS is similar to that in newborns delivered vaginally.

Pulmonary volume measurements during high-frequency jet ventilation in anesthetized man.

To assess the validity of indirect spirometry during conventional intermittent positive-pressure ventilation (IPPV) and high-frequency jet ventilation (HFJV), we measured changes in functional residual capacity (delta FRC) and tidal volume (VT) with two external strain gauges in eight sedated and paralyzed patients. The thoracic and abdominal gauges were calibrated simultaneously in quasi-static and dynamic conditions. The delta FRC measured during HFJV (1 to 5 Hz) and the VT measured during IPPV (0.25 Hz) were found to be equivalent by the two gauges in most patients (r = .90 and r = .99, respectively), but no correlation was found between the VT values inferred by each gauge in HFJV (r = .54). During HFJV, spectral analysis of the gauge signals showed important damping of the abdominal motion (AB) and an amplification of the thoracic displacements (RC) in four patients when measurements were taken at greater than 3 Hz. We conclude that, provided the partition of the volume between AB and RC remains constant, indirect spirometry may measure VT in IPPV and delta FRC in HFJV, but it fails to measure VT accurately during HFJV.

Alkalinization of 0.5% lidocaine for intravenous regional anesthesia.

Although remaining a controversial issue, alkalinization of lidocaine or bupivacaine may shorten the time to onset and increase the duration of the sensory block. The aim of this study was to evaluate the effect of pH adjustment on the sensory and motor blocks during intravenous regional anesthesia (IVRA) with lidocaine. Thirty-one patients scheduled for minor hand surgery performed under IVRA were randomized into two groups: Group 1 (n = 14): 1% lidocaine, 3 mg/kg, diluted with the same volume of physiological saline solution (pH = 6.63 +/- 0.05), and Group 2 (n = 17): 1% lidocaine, 3 mg/kg, diluted with the same volume of 1.4% sodium bicarbonate (pH = 7.34 +/- 0.05). final concentration of lidocaine was thus 0.5% in both groups. Sensory block was assessed by pinprick every 2 minutes in areas corresponding to six terminal nerves: ulnar, median, radial, musculocutaneous, medial cutaneous nerve of arm and intercostobrachial, and medial cutaneous nerve of forearm. The time between release of tourniquet (at the end of surgery) and appearance of pain was recorded. Motor blockade was evaluated by asking the patient to squeeze strongly a blood pressure cuff previously inflated to 40 mmHg. This maneuver was performed before and every 2 minutes after injection. No statistical differences were found between the two groups whatever the parameter studied. In conclusion, there is no advantage (over plain solutions) to using pH-adjusted lidocaine during IVRA for hand surgery.

Spread of analgesia and ventilatory response to carbon dioxide following epidural somatostatin.

The effects of somatostatin, injected into the epidural space, on analgesia and control of ventilation were studied in 25 patients aged 41 +/- 9 yrs (mean +/- SD). The patients were allocated to three groups to receive: Group I--1 mg of somatostatin in 2 ml saline (n = 13); Group II--1 mg of somatostatin in 10 ml saline (n = 6); and Group III--somatostatin in a loading dose of 250 micrograms followed by an infusion of 125 micrograms h-1 (n = 6). Segmental cutaneous analgesia, assessed by pinprick, without loss of thermal sensibility or motor blockade was found in all patients. Onset times and durations of analgesia were 15 +/- 2 min and 69 +/- 19 min (mean +/- SD) in Group I and 14 +/- 2 min and 68 +/- 11 min in Group II. The extent of dermatome analgesia at 30 min and 60 min after somatostatin injection, respectively, was: T6 +/- 2 to T12 +/- 1, T4 +/- 2 to L1 +/- 2 in Group I, and T7 +/- 3 to L1 +/- 3, T3 +/- 1 to T12 +/- 2 in Group II. Continuous analgesia with onset of 16 +/- 2 min and extending from T7 +/- 1 to T12 +/- 1 was observed in Group III. No side-effects were observed. The control of ventilation studies in eight patients in Group I by the Read's rebreathing method did not show any significant change.

Analgesia and ventilatory response to CO2 following epidural sufentanil in children.

The authors studied the effects of epidural sufentanil (0.75 microgram.kg-1) after urologic surgery in 15 children ranging in age from 4 to 12 yr, and in weight from 14 to 47 kg. The onset and duration of analgesia were 3.0 +/- 0.3 and 198 +/- 19 min, respectively (mean +/- SEM). Side effects included pruritus (3/15), nausea and vomiting (5/15), drowsiness (10/15), and urinary retention (1/11). No apnea was observed. Periosteal analgesia and ventilation were studied in eight of the children (mean age 8.6 +/- 0.8 yr). There was significant periosteal analgesia of the tibia (30, 60, 90, and 120 min after injection) and of the radius (60, 90, and 120 min after injection). Resting respiratory rate and tidal volume did not change during the study. Resting minute-ventilation decreased from 6.3 +/- 0.5 l.min-1 preoperatively to 5.6 +/- 0.6 l.min-1 (P less than 0.05) postoperatively, before epidural sufentanil injection; it did not decrease further after epidural sufentanil. Similarly, end-tidal CO2 tension increased significantly from 37.2 +/- 0.7 mmHg preoperatively to 39.9 +/- 1.2 mmHg (P less than 0.05) postoperatively, before epidural sufentanil; epidural sufentanil did not cause a further significant increase in end-tidal CO2 tension. The slope of the CO2 ventilatory response curve decreased significantly from 1.68 +/- 0.12 l.min-1. mmHg-1 preoperatively to 1.10 +/- 0.13 l.min-1.mmHg-1 (P less than 0.01) postoperatively. There were further significant decreases to 0.68 +/- 0.10 and 0.89 +/- 0.16 l.min-1.mmHg-1 30 and 60 min after epidural sufentanil.(ABSTRACT TRUNCATED AT 250 WORDS)