Prostacyclin in experimental septic acute respiratory failure

Manipulation of prostaglandins (PG) in animal models of sepsis and acute respiratory failure (ARF) is promising. Prostacyclin (PGI2), a short-acting vasodilator, was evaluated in a porcine model of ARF produced by continuous infusion of live Pseudomonas aeruginosa (Ps.). Cardiopulmonary parameters were monitored in three groups of spontaneously breathing animals that received 0.1 micrograms PGI2/kg/min begun 20 min after baseline (Group I); 2 X 10(8) Ps./20 kg/min (Group II); identical Ps. infusion and then PGI2 begun at 20 min (Group III). The decrease in mean arterial blood pressure and cardiac index with Ps. infusion was improved by PGI2 treatment. In Groups II and III, mean pulmonary artery pressure (PAP) doubled (P less than 0.005) and pulmonary vascular resistance (PVR) tripled (P less than 0.01) by 15 min. Both PAP and PVR were decreased significantly with PGI2 treatment. In both Ps. groups, significant hypoxemia occurred. PGI2 improves cardiac output and acts as a pulmonary vasodilator, but does not improve oxygenation in this porcine model of severe ARF.     

Effect of an anti-C5a monoclonal antibody indicates a prominent role for anaphylatoxin in pulmonary xenograft dysfunction

BACKGROUND: In contrast to renal or cardiac xenografts, the inhibition of complement using cobra venom factor (CVF) accelerates pulmonary xenograft failure. By activating C3/C5 convertase, CVF depletes complement while additionally generating C5a and other anaphylatoxins, to which pulmonary xenografts may be uniquely susceptible. The current study investigates the role of C5a in pulmonary xenograft failure in baboons. METHODS: Left orthotopic pulmonary xenografts using swine lungs expressing human CD46 were performed in baboons receiving: I) no other treatment (n=4), II) immunodepletion (n=5), and III) immunodepletion plus a single dose of mouse anti-human C5a monoclonal antibody (anti-C5a, 0.6 mg/kg administered intravenously) (n=3). The extent to which anti-C5a inhibits baboon C5a was assessed in vitro using a hemolytic reaction involving baboon serum and porcine red blood cells and by ELISA. RESULTS: Baboons in Group III exhibited significantly prolonged xenograft survival (mean=722+/-121 min, P=0.02) compared to baboons in Group I (mean=202+/-24 min) and Group II (mean=276+/-79 min). Furthermore, baboons in Groups I and II experienced pronounced hemodynamic compromise requiring inotropic support whereas those in Group III remained hemodynamically stable throughout experimentation without the need for additional pharmacologic intervention. CONCLUSIONS: These findings indicate that C5a exacerbates pulmonary xenograft injury and compromises recipient hemodynamic status. Moreover, blockade of anaphylatoxins, such as C5a, offers a promising approach for future investigations aimed at preventing pulmonary xenograft injury in baboons.     

Effects of ibuprofen on a porcine model of acute respiratory failure

Blockade of the arachidonic acid cascade has been shown to improve survival and hemodynamic alterations in animal models of sepsis and acute respiratory failure (ARF). The effects of intravenous ibuprofen, a cyclooxygenase inhibitor, were observed in 20-30 kg pigs with ARF induced by a continuous LD100 infusion of live Pseudomonas aeruginosa (2 X 10(8)/20 kg/min). Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250-ml tidal volume and 0.5 FiO2. Pigs were randomly assigned to three groups: Group I received 2 bolus infusions of ibuprofen (12.5 mg/kg) at 20 and 210 min after baseline; Group II had Ps. aeruginosa (2 X 10(8) CFU/20 kg/min) only; Group III received Ps. aeruginosa and 12.5 mg/kg of ibuprofen at 20 and 210 min of ARF. Ibuprofen alone caused no significant changes in cardiorespiratory parameters. With Ps. aeruginosa infusion, significant pulmonary hypertension, hypoxemia, increased intrapulmonary shunt fraction, and systemic hypotension occurred. In the septic animals treated with ibuprofen, oxygenation was improved by a significant decrease in shunt, pulmonary edema, and pulmonary hypertension.     

Systemic haemodynamic and metabolic effects of deliberate hypotension with isoflurane anaesthesia or sodium nitroprusside during total hip arthroplasty

Isoflurane (ISO) was examined as an alternative hypotensive agent to nitroprusside (SNP) in 16 patients (mean age: 60 years) anaesthetized for total hip arthroplasty. MAP was decreased to 50 per cent of the awake level by infusion of SNP in Group I (n = 8) and with ISO in Group II (n = 8). Fentanyl (10-16 micrograms X kg-1) was administered to both groups. Haemodynamic measurements were repeated in the lateral position before, during and after hypotension. Polygeline and fresh frozen plasma were infused throughout the study period in volumes sufficient to maintain pulmonary capillary wedge pressure in the 7-9 mmHg range. The MAP decrease was the same in both groups, as were perioperative blood replacement (mean 500 ml), and postoperative haematocrits. Total perioperative fluid replacement was higher (p less than 0.01) in Group I (mean 2500 ml) than in Group II (mean 1300 ml). Venous tone was more affected by SNP than by ISO. ISO decreased the systemic vascular resistance index and oxygen consumption (VO2) without any change in CI or in Qs/Qt, in contrast to SNP which increased CI, VO2 and Qs/Qt.     

Pre-treatment of donor with 1-deamino-8-d-arginine vasopressin could alleviate early failure of porcine xenograft in a cobra venom factor treated canine recipient.

OBJECTIVE: Unlike cardiac or renal xenotransplants, the depletion of complement using cobra venom factor (CVF) does not improve pulmonary xenograft survival. Several cases suggest that the swine von Willebrand factor (vWF) may play a major role in presenting a different pathogenesis of pulmonary xenograft dysfunction from other organs. To evaluate the role of vWF and the complement system in mediating hyperacute vascular injury of pulmonary xenografts and elucidate pathogenesis of the injury, we performed swine-to-canine orthotropic single lung xenotransplantation after pre-treatment of 1-deamino-8-d-arginine vasopressin (DDAVP) and CVF. METHODS: We set up three groups for lung xenotransplantation: group I served as the control group; group II, recipients pre-treated with CVF; group III, donors pre-treated with DDAVP (9 mg/kg, 3 days)/recipients pre-treated with CVF (60 u/kg). Hemodynamic data, coagulation and complement system parameters, and grafted lung pathologies were examined serially for 3h after transplantation. RESULTS: DDAVP infusion reduced the vWF content in swine lung tissue in vivo (7.7+/-2.4 AU/mg vs 16.0+/-5.6 AU/mg, P < 0.0001). Infusion of CVF 24 h prior to transplantation effectively depleted the recipient's serum C3 and complement hemolytic activity below the detectable range. Regardless of the use of CVF, both groups I and II transplanted with unmodified grafts showed an immediate drop in leukocytes and platelet counts after transplantation. However, in group III, in recipients transplanted with DDAVP pre-treated swine lung, the platelet count did not decrease after transplantation (P = 0.0295). The decrease of plasma antithrombin and fibrinogen tended to be attenuated in group III. Light microscopic examination revealed extensive vascular thromboses in both capillary and larger vessels, as well as early pulmonary parenchymal damage in groups I and II, but were rarely observed in group III. CONCLUSIONS: Complement inhibition alone was not enough to alleviate intravascular thrombosis, the main pathology in pulmonary xenotransplantation. Pre-infusion of DDAVP to the donor animal was effective in preventing platelet sequestration and attenuated intravascular thrombosis. It is suggested that the strategies targeting vWF would be promising for successful pulmonary xenotransplantation.     

Effects of a bradykinin B(2) receptor antagonist, FR173657, on pulmonary ischemia-reperfusion injury in dogs.

BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on pulmonary ischemia-reperfusion (I/R) injury. METHODS: Twenty-four mongrel dogs were divided into four groups (n = 6 each). In Groups I, II and III, FR doses of 33, 100 and 300 nmol/kg per hour, respectively, were administered continuously beginning 30 minutes before ischemia and continuing for 2 hours after reperfusion. In Group IV, vehicle alone was administered. Warm ischemia was induced for 3 hours by clamping the left pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected and then anastomosed before reperfusion. Fifteen minutes after reperfusion, the right pulmonary artery and bronchus were ligated. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and the alveolar - arterial oxygen pressure difference (A-aDO2) were measured for 4 hours after reperfusion. Lung tissue was harvested for wet-to-dry weight ratio (WDR) measurements, histopathologic studies and polymorphonuclear neutrophil (PMN) counts. Serum thromboxane (TX) B(2), 6-keto-prostaglandin (PG) F(1alpha) and leukotriene (LT) B(4) levels were also measured. RESULTS: PaO(2), A-aDO2, L-PVR and CO were significantly (p < 0.05) improved and WDR was significantly (p < 0.05) lower in Groups II and III than in Group IV. Histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced in Groups I, II and III compared with Group IV. TXB(2) levels were significantly (p < 0.05) lower in Group II than in Group IV, whereas 6-keto-PGF(1alpha) levels were not significantly different. LTB(4) levels were significantly (p < 0.05) lower in Groups II and III than in Group IV. CONCLUSIONS: FR appears to have a protective effect on pulmonary I/R injury stemming from the inhibition of eicosanoid release.     

Acute cardiopulmonary effects of nitroglycerin in canine oleic acid pulmonary edema

In a canine model of acute respiratory failure, the authors investigated acute cardiopulmonary effects of nitroglycerin (TNG) and compared the results with those obtained after phlebotomy. Oleic acid increased intrapulmonary shunt (Qs/Qt) from 7.4 to 31% (P less than 0.001) and decreased (P less than 0.01) cardiac output (CO). In the presence of assumed low-pressure pulmonary edema, TNG was infused to decrease mean blood pressure (BP) by 40%; this was associated with a 26% decrease (P less than 0.05) in CO. Qs/Qt increased from 31 to 42% (P less than 0.01). There was a slight increase (P less than 0.01) in pulmonary vascular resistance (PVR) with TNG, and mean pulmonary artery pressure (PAP) decreased (P less than 0.05). In contrast, when CO was decreased by a similar amount with phlebotomy, mean Qs/Qt did not significantly change. There were similar changes in PVR and PAP and mixed venous O2 tension with TNG and phlebotomy. Accordingly, current results rule out increased flow, increased PVO2, and mechanical alterations in pulmonary vascular pressures as contributory to the increase in Qs/Qt with TNG. Alternatively, the increase in Qs/Qt with TNG may be explained by a direct pharmacologic decrease in pulmonary hypoxic vasoconstriction and/or by nonspecific pharmacologic effects.     

The ineffectiveness of steroid therapy for treatment of fresh-water near-drowning.

The authors evaluated the efficacy of continuous positive-pressure ventilation (CPPV) and methylprenisolone alone and in combination as therapy for near-drowning in 80 dogs that had aspirated distilled water (22 ml/kg or 44 ml/kg). Forty dogs were treated with mechanical ventilation for one hour and 40 for 24 hours. Blood-gas tensions, pH, cardiac output and intrapulmonary shunt (Qs/Qt) were measured frequently for 24 hours. Blood-gas tensions and pH were again measured 48 and 72 hours and seven days later in survivors. Arterial oxygen tension (PaO2) decreased and Qs/Qt increased in all animals following aspiration and before therapy. Forty dogs received methylprednisolone intravenously (30 mg/kg) (20 breathed spontaneously and 20 had CPPV). There was a significant increase in PaO2 and decrease in pulmonary shunt in dogs that were ventilated mechanically compared with animals that breathed spontaneously. Treatment with methylprednisolone made no difference in blood gases, pulmonary shunt, or survival rates. Thus, no evidence to support the use of methylprednisolone in the treatment of the pulmonary lesion of fresh-water near-drowning was found. (Key words: Drowning, fresh-water; Hormones, adrenal, methylprednisolone.)     

安氟醚对肺血分流的影响

２０例行上腹部手术忠者，随机分为实验组和对照组，每组１０例。实验组在硬膜外阻滞下，吸入６０％Ｎ２Ｏ－４０％Ｏ２基础上吸入１．６％安氟醚。分别在麻醉前、插管后０．５小时，吸安氟醚１小时、２小时，停安氟醚０．５小时，拔管后吸空气１小时取动脉及右心室混合静脉血进行血气分析，计算分流量。结果表明实验组在吸安氟醚后肺内分流增加，明显高于对照组（Ｐ＜０．０５）。结论是安氟醚使肺内分流增加，并持续至手术后一段时间，可导致低氧血症，应予吸氧预防。     

Continuous dose furosemide as a therapeutic approach to acute respiratory distress syndrome (ARDS)

BACKGROUND: Acute respiratory distress syndrome (ARDS) is seen in a variety of clinical settings in critically ill patients. ARDS has been defined as a clinical syndrome characterized by progressive hypoxemia, tachypnea, and generalized patchy bilateral pulmonary infiltrates in the absence of cardiac failure. Furosemide has been shown to improve pulmonary gas exchange and intrapulmonary shunt in animal models of ARDS by preferential perfusion of nonedematous lung units. We hypothesized that continuous dose furosemide would improve lung injury during resuscitation from oleic acid-induced lung injury in canines. METHODS: Ten mongrel dogs were anesthetized and given intravenous oleic acid (0.1 mg/kg) to induce lung injury. Once lung injury was established (2 h) the control animals (n = 6) were continued on standard supportive therapy, and the study animals (n = 4) were started on continuous dose furosemide at 0.2 mg/kg/h. Cardiac filling pressures were maintained in all animals by infusion of isotonic saline solution. Data collected included lung injury score (LIS), cardiac index (CI), stroke volume index (SVI), pulmonary capillary wedge pressure (PCWP), urine output (UO), volume of resuscitation (VR), and pulmonary shunt fraction (Qs/Qt). Data were collected at baseline, established lung injury (2 h), and end of protocol (6 h). Data were compared between groups at various stages of the model using one-way analysis of variance with repeated measures. RESULTS: All 10 animals survived the protocol. There was no difference between the experimental and control groups at baseline or established lung injury (2 h) for CI, SVI, PCWP, or VR. There was a significant improvement in PO2/FIO2 and reduction of PEEP values in the furosemide group. There was also a statistically significant difference between experimental and control groups in LIS, Qs/Qt, and urine volumes. CONCLUSIONS: Continuous dose furosemide therapy improves LIS, PO2/FIO2, and Qs/Qt and decreases PEEP requirements in this oleic acid model of ARDS.     

The use of esmolol and magnesium to prevent haemodynamic responses to extubation after coronary artery grafting

BACKGROUND AND OBJECTIVE: The haemodynamic responses during extubation can cause complications after open-heart surgery. In this study, we aimed to examine the effect of esmolol and magnesium before extubation on these haemodynamic responses. METHODS: Following the approval of local Ethics Committee, 120 patients having coronary artery bypass grafting with extubation in the intensive care unit were included in the study. Patients were allocated to receive esmolol 1 mg kg-1 (group I, n = 40), magnesium 30 mg kg-1 (Group II, n = 40) or normal saline (Group III, n = 40). Study medication was administered as a 20-min infusion in a volume of 20 mL. Patients were extubated just after termination of the infusion. Heart rate, blood pressure and central venous pressure were recorded prior to drug administration, before extubation, during extubation and 1 min after extubation. RESULTS: Heart rate was lower in Group I than in Groups II (P < 0.05) and III (P < 0.001) and lower in Group II than in Group III (P < 0.05) during extubation. It was also lower in Group I than in Group III (P < 0.05) after extubation. Systolic blood pressure was lower in Group I than in Groups II and III (P < 0.001) during extubation. Diastolic blood pressure was higher in Group III than in Groups I and II during extubation (P < 0.001) and after extubation (P < 0.05). Mean arterial pressure was lower in Group I than in Groups II and III (P < 0.001) during extubation, lower in Group II than in Group III (P < 0.05) during extubation and lower in Group I than in Group III (P < 0.05) after extubation. CONCLUSION: We found that using esmolol before extubation following coronary artery bypass graft surgery prevents undesirable haemodynamic responses while magnesium reduces undesirable haemodynamic responses but does not prevent them.     

单肺通气期间麻醉期用药对肺内分流的影响

背景 低氧血症是单肺通气(one lung ventilation,OLV)期间最常见的并发症.缺氧性肺血管收缩(hypoxic pulmonary vasoconstriction,HPV)是肺血管对局部低氧分压的反射性收缩,可以减少肺内分流(pulmonary shunt fraction,Qs/Qt)、维持动脉血氧分压(partial pressure of arterial oxygen,PaO2)、防止低氧血症的发生.目的 探讨OLV期间麻醉期用药对Qs/Qt的影响,指导临床应用.内容 综述OLV期间麻醉期用药对机体HPV、Qs/Qt和PaO2的影响.趋向 OLV期间麻醉期用药可以对HPV产生抑制或增强作用,从而影响Qs/Qt和PaO2.临床上要避免使用抑制HPV作用、增加Qs/Qt的药物,防止患者出现低氧血症.     

The primary action of epidural fentanyl after cesarean delivery is via a spinal mechanism

We tested the hypotheses that the primary mechanism of action of epidural fentanyl after cesarean delivery is spinal and that very small dose epidural bupivacaine with epinephrine enhances this effect. After elective cesarean delivery, 100 parturients were randomized in a double-blinded design to four groups. Group I and II patients received a continuous 12 mL/h epidural infusion of bupivacaine 0.015% with epinephrine 1 microg/mL for 48 h and Groups III and IV received a 12 mL/h saline epidural infusion instead. Fentanyl 20 microg/mL was administered via a patient-controlled analgesia device either into the epidural infusion (Groups I and IV) or IV (Groups II and III). When compared to patients receiving epidural fentanyl, those receiving IV fentanyl required larger mean infused and total dose of fentanyl (P < 0.0001), reported more pain (P < 0.001), and had a more frequent incidence of excessive sedation (P < 0.01), nausea (P < 0.01), and vomiting (P < 0.01). Plasma concentrations of fentanyl were larger for Group II and III than for Groups I and IV (P < 0.001) at 24 and 48 h. Our results support the hypothesis that the primary mechanism of analgesia of epidural fentanyl after cesarean delivery is spinal. Our data also show that the total required dose of epidural, but not IV, fentanyl is reduced by very small dose epidural bupivacaine and epinephrine (Group I versus Group IV, P < 0.02 and Group II vs Group III, not significant). IMPLICATIONS: Fentanyl administered epidurally to parturients after cesarean delivery has a primarily spinal mechanism of action and this effect is enhanced by very small dose epidural bupivacaine and epinephrine.     

Intrapulmonary shunting during deliberate hypotension with nifedipine, diltiazem and labetalol in dogs

Pulmonary shunt (Qs/Qt) was calculated in 49 mongrel dogs weighing 18-20 kg during mechanical ventilation, before and during deliberate hypotension with either nifedipine (group N), diltiazem (group D), labetalol (group L), or ethyl alcohol and polyethylene glycol (group E). A 30 per cent decrease in mean arterial blood pressure occurred after two minutes of nifedipine infusion, two minutes after diltiazem, and three minutes after labetalol; these effects lasted two hours after nifedipine administration, 90 minutes after diltiazem and three hours after labetalol. There was an accompanying significant decrease in systemic and pulmonary vascular resistance. Qs/Qt and cardiac output increased significantly after nifedipine infusion. Shunt increased (mean +/- S.E.) from 9.7 +/- 0.8 to 18.25 +/- 1.05 per cent at two minutes (p less than 0.0005); 19.05 +/- 1.2 per cent at 30 minutes (p less than 0.005); 17.5 +/- 1.6 per cent at two hours (p less than 0.01); and 12 +/- 1.1 per cent at three hours (p less than 0.025). No increase in shunt occurred after the administration of diltiazem, labetalol or polyethylene glycol and ethyl alcohol. Arterial oxygen tension (PaO2) decreased significantly after nifedipine infusion from 146 +/- 11.5 to 105 +/- 3.5 mmHg two minutes after infusion; to 89.5 +/- 3 mmHg 30 minutes after; 115 +/- 4.75 mmHg two hours after; and 130 +/- 10.75 mmHg three hours later. PaO2 was not significantly different after diltiazem, labetalol, or polyethylene glycol and ethyl alcohol administration. With nifedipine cardiac output increased from 2.25 +/- 0.3 to 3.95 +/- 0.25 after two minutes (p less than 0.005) to 3.85 +/- 0.35 after 30 minutes (p less than 0.005), 3.7 +/- 3 after two hours (p less than 0.01) to 2.9 +/- 1.1 after three hours. No significant increase in cardiac output occurred in groups D or L. These results suggest that only nifedipine infusion significantly alters oxygenation in dogs and therefore its use warrants caution in the presence of a preexisting abnormal Qs/Qt.     

Hemodynamic and morphologic alterations after experimental administration of protamine sulfate

The hemodynamic, hematologic, and morphologic effects induced by protamine sulfate have been studied in 28 dogs divided into 6 groups. All of the groups were given heparin (3 mg/kg body weight) and Groups I, II, III, and IV were given protamine (5 mg/kg body weight). Group I (control group) was not subjected to extracorporeal circulation. The other groups had the following interventions: Group II, cardiopulmonary bypass without aortic clamp, hypothermia, or cardioplegia; Groups III and V, hypothermia of 25 degrees C, aortic clamping for 25 minutes, administration of cardioplegic solution, and slow rewarming; and Groups IV and VI, the same as Groups III and V, but with rapid rewarming. After injection of protamine sulfate, there was a decrease in mean arterial pressure due to peripheral vasodilation and an increase in the mean pulmonary pressure due to increased pulmonary vascular resistance; marked diminution of the number of circulating platelets aside from the extracorporeal circulation; a decrease in the contractility of both ventricles with augmented right ventricular work and decreased cardiac output; and right ventricular edema in Groups I, II, III, and IV. These alterations were most evident in Groups III and IV.     

Comparative hemodynamic effects of selective superior mesenteric arterial and peripheral intravenous glucagon infusions

This experiment was designed to determine whether any hemodynamic benefits attend administration of equal pharmacologic doses of glucagon (1 micrograms/kg/m) by continuous intravenous infusion (Group I, n = 6) versus selective intraarterial infusion (Group II, n = 6) via the superior mesenteric artery (SMA) in dogs. Cardiac output, heart rate, mean arterial pressure, total peripheral resistance, pulmonary vascular resistance, superior mesenteric artery flow (SMAQ), SMA vascular resistance, and portal venous pressure were measured at baseline (BL) and at 5, 15, 30, and 45 min during glucagon infusion. SMAQ virtually doubled at 5 min from a baseline of 570 +/- 60 ml/min to 1158 +/- 146 ml/min in Group I (P less than 0.001), and from a baseline of 527 +/- 171 to 1018 +/- 331 ml/min in Group II (P less than 0.002). SMAQ was significantly higher in Group I at 30 and 45 min compared to Group II (P less than 0.03) despite similar peripheral plasma glucagon levels. SMA vascular resistance was significantly lowered in both groups, with a greater reduction occurring during intravenous glucagon administration at 45 min (P less than 0.05). Changes in systemic hemodynamic parameters, as well as glucagon and glucose levels were not statistically different between Groups I and II at any time period. Glucagon is a potent mesenteric vasodilator and the resultant profound splanchnic hemodynamic effects are as marked during intravenous administration as during selective SMA infusion.     

Evaluation of (1-sarcosine, 8-isoleucine) angiotensin II as a therapeutic agent for oleic acid-induced pulmonary edema

(1-Sarcosine, 8-isoleucine) angiotensin II was assessed as a therapeutic agent for acute respiratory distress syndrome with oleic acid pulmonary edema in sheep used as an experimental model. Under general anesthesia with controlled mechanical ventilation with 100% oxygen, 32 sheep received oleic acid (0.075 ml/kg) intravenously. After oleic acid infusion, 20 animals were treated with continuous intravenous infusion of the angiotensin II analogue; nine received 300 ng/kg/min, six received 600 ng/kg/min, and five received 2000 ng/kg/min. Cardiopulmonary measurements were repeated every 30 minutes for 270 minutes. According to time-integrated PaO2, six of 15 animals of the groups given 300 and 600 ng/kg/min (43%) did not respond to the treatment. All animals responded in the group given 2000 ng/kg/min. Animals in the latter group had lower Qs/Qt, PaCO2, and airway resistance than had the control animals. Elevation of pulmonary vascular resistance was limited and mean arterial blood pressure was well maintained. These results reveal that (1-Sar, 8-Ile) angiotensin II is effective in the treatment of oleic acid-induced pulmonary edema.     

Propofol decreases diaphragmatic contractility in dogs

Volatile anesthetics depress diaphragmatic muscle function; however, no data are available regarding the effect of propofol on diaphragmatic contractility. We therefore studied this effect in dogs. Pentobarbital-anesthetized animals were divided into three groups of 10 each. Group I received only maintenance fluid; Group II was infused with a subhypnotic dose of propofol (0.1-mg/kg initial dose plus 1.5-mg x kg(-1) x h(-1) maintenance dose); Group III was infused with an anesthetic dose of propofol (0.1-mg/kg initial dose plus 6.0-mg x kg(-1) x h(-1) maintenance dose). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). With an infusion of propofol in Groups II and III, Pdi at low-frequency (20-Hz) stimulation decreased from the baseline values (P < 0.05), whereas Pdi at high-frequency (100-Hz) stimulation did not change. Compared with Group I, Pdi at 20-Hz stimulation decreased during propofol administration in Groups II and III (P < 0.05). The decrease in Pdi was more in Group III than in Group II (P < 0.05). We conclude that propofol is associated with a dose-related inhibitory effect on diaphragmatic contractility in dogs. IMPLICATIONS: Propofol is an effective IV anesthetic for the induction and maintenance of anesthesia. Subhypnotic and anesthetic doses of propofol decrease diaphragmatic contractility in dogs.     

A sevoflurane induction of anesthesia with gradual reduction of concentration is well tolerated in elderly patients

PURPOSE: To establish the appropriate inhalation induction technique using a high concentration of sevoflurane in the elderly. METHODS: Forty-five patients, aged 70-79-yr-old, were randomly divided into three groups: 1) Group I: anesthesia was induced with propofol 2 mg x kg(-1) and sevoflurane 2% (n = 15); 2) Group II: anesthesia was induced with a three- minute inhalation of sevoflurane 8%; 3) Group III: anesthesia was induced with inhalation of sevoflurane using a gradual reduction technique (8, 6, 4% for each minute). In Groups II and III, a modified vital capacity inhalation induction was performed. Mean arterial pressure (MAP), heart rate (HR) and oxygen saturation (SpO(2)) were measured continuously during induction. In addition, induction time and adverse events related to anesthetic induction were recorded. RESULTS: The induction time in Group I was significantly shorter than that in Groups II and III (P < 0.05). However, there was no difference in the induction time between Groups II and III. In Groups II and III, the majority of patients required additional breaths. In comparison with the other groups, stability of MAP was maintained in Group III. The variations of HR in all groups were small. During induction, no patient experienced a decrease in SpO(2) below 96%, except for two patients in Group I. Severe respiratory adverse events were not observed. Other adverse events were similar in all groups. CONCLUSIONS: Our results suggest that a high concentration sevoflurane induction using a gradual reduction technique may be an acceptable alternative to standard iv induction in elderly patients.     

Complement Activation and its Relationship to Adult Respiratory Distress Syndrome. An Experimental Study in Pigs

Pulmonary leucostasis induced by complement activation has been considered an important pathogenic factor in adult respiratory distress syndrome (ARDS). To determine whether complement activation per se could evoke pulmonary dysfunction similar to ARDS, pigs were repeatedly infused with complement-activated plasma (CAP). Complement activation was produced by incubation of plasma with zymosan. Three groups of animals were investigated. Control animals received non-activated plasma. Nine animals (Group II) were given four infusions of GAP at a rate of 7 ml min^-1, and another nine animals (Group III) received two CAP infusions at a rate of 7 ml min^-1 followed by two at a rate of 14 ml min^-1. In the control animals there were no changes in gas exchange or haemodynamic variables and the leucocyte counts gradually increased. Infusion of CAP resulted in transient peripheral leucopenia and a dose-rate-dependent reversible increase in pulmonary vascular resistance in all animals. In one animal of Group II and in six of Group III there was a significant infusion-related decrease in PaO₂ due to increased venous admixture. These animals were characterized by an enhanced pulmonary vascular tone before the start of the first CAP infusion. They also displayed a more pronounced pulmonary vascular response to infusion of CAP. The changes in gas exchange variables and pulmonary haemodynamics showed no relation to the degree of leucopenia or decrease in platelet count. The increased venous admixture was caused by "dry" ventilation/perfusion mismatching and not by oedema. These results suggest that additional factors besides complement activation and pulmonary leucostasis are required for the development of increased microvascular permeability and the pulmonary oedema characterizing ARDS.