Major abdominal surgery for cancer: does epidural analgesia have a long-term effect on recurrence-free and overall survival?

BACKGROUND: Retrospective studies have suggested that regional analgesia combined with general anaesthesia could decrease cancer recurrence. The purpose of this study was to assess the influence of regional analgesia on recurrence-free (RFS) and overall survival in patients undergoing major intra-abdominal surgery for cancer. METHOD: Patients previously included in a prospective randomized study comparing two postoperative techniques of analgesia were retrospectively studied. The EP group received general anaesthesia with bupivacaine thoracic epidural analgesia and the SC group received general anaesthesia with fentanyl followed by continuous subcutaneous morphine. RESULTS: One hundred and thirty-two patients were analyzed (63 and 69 in SC and EP group, respectively) with a 17-year-median follow-up. After 5 years, RFS was 43% [95% CI: 32%-55%] in EP group and 24% [95% CI: 15%-36%] in SC group, but the difference did not reach statistical significance for RFS nor for overall survival (P=0.10 and 0.16 respectively). Using multivariable analysis over the whole follow-up period, the type of analgesia was not a statistically significant predictive factor for RFS (EP/SC, HR=1.3 [95% CI: 0.8-2.0%]). The anaesthesia effect changed moderately over the follow-up and HR for overall survival (EP/SC) reached statistical significance after 5, 6 and 8 years. CONCLUSION: Despite a trend in favour of the epidural, this retrospective review of patients included in a previous randomized study failed to demonstrate a statistically significant association between the perioperative analgesia and RFS after abdominal surgery for cancer. The duration of follow-up may have an impact on the analgesia effect on survival.

Hypersensitivity reactions to Patent Blue V in breast cancer surgery: a prospective multicentre study.

BACKGROUND: An increasing number of immediate hypersensitivity reactions (HSR) have been reported after the use of Patent Blue V (PBV) for breast cancer surgery. This is the first study to publish prospective data with systematic allergological assessment. METHODS: We conducted a multicentre study in 10 French cancer centres for over 6 months. All patients scheduled for breast surgery with injection of PBV were included in the study. Patients were screened for past medical history, atopy, and known food and drug allergies. When suspected HSR or unexplained reactions occurred after injection of PBV, blood samples were taken, and plasma histamine and serum tryptase concentrations were measured. HSR to PBV was suggested if skin tests performed 6 weeks later were positive. RESULTS: Nine suspected HSR to PBV were observed in 1742 patients. Skin tests were positive in six patients, giving an incidence of 0.34%. Four grade I and two grade III HSR were observed, both requiring intensive care unit treatment. Mean onset time of the reaction was 55 ± 37 min. Plasma histamine was elevated in four patients, while serum tryptase was normal. We found no risk factors associated with HSR to PBV. CONCLUSION: An incidence rate of one in 300 HSR to PBV was observed for patients exposed to PBV during sentinel lymph node detection. This rate is higher than rates reported after the use of neuromuscular blocking agents, latex or antibiotics.

[Panniculectomy as first part of colorectal resection for cancer in a morbidly obese patient]. / La panniculectomie première comme voie d'abord dans la résection colorectale pour cancer chez le grand obèse.

We reported the case of a patient presenting a rectal cancer of the upper part with a BMI at 59 which was previously considered as a contraindication to surgery. To perform the operation we had to make as first step of the procedure a panniculectomy. The technique made possible the rectal resection under good conditions, without blood transfusion. The post-operative course was uneventful except a pulmonary embolism controlled with medical treatment. This procedure is feasible in colorectal surgery.

Mechanisms of TNF-alpha stimulation of amiloride-sensitive sodium transport across alveolar epithelium.

Because tumor necrosis factor (TNF)-alpha can upregulate alveolar fluid clearance (AFC) in pneumonia or septic peritonitis, the mechanisms responsible for the TNF-alpha-mediated increase in epithelial fluid transport were studied. In rats, 5 microg of TNF-alpha in the alveolar instillate increased AFC by 67%. This increase was inhibited by amiloride but not by propranolol. We also tested a triple-mutant TNF-alpha that is deficient in the lectinlike tip portion of the molecule responsible for its membrane conductance effect; the mutant also has decreased binding affinity to both TNF-alpha receptors. The triple-mutant TNF-alpha did not increase AFC. Perfusion of human A549 cells, patched in the whole cell mode, with TNF-alpha (120 ng/ml) resulted in a sustained increase in Na(+) currents from 82 +/- 9 to 549 +/- 146 pA (P < 0.005; n = 6). The TNF-alpha-elicited Na(+) current was inhibited by amiloride, and there was no change when A549 cells were perfused with the triple-mutant TNF-alpha or after preincubation with blocking antibodies to the two TNF-alpha receptors before perfusion with TNF-alpha. In conclusion, although TNF- alpha can initiate acute inflammation and edema formation in the lung, TNF-alpha can also increase AFC by an amiloride-sensitive, cAMP-independent mechanism that enhances the resolution of alveolar edema in pathological conditions by either binding to its receptors or activating Na(+) channels by means of its lectinlike domain.

Biting the laryngeal mask: an unusual cause of negative pressure pulmonary edema.

PURPOSE: To describe negative pressure pulmonary edema due to biting of the laryngeal mask tube at emergence from general anesthesia. CLINICAL FEATURES: A healthy patient underwent general anesthesia using a laryngeal mask airway and mechanical ventilation. During recovery, the patient strongly bit the laryngeal mask and made very forceful inspiratory efforts until the mask was removed. Five minutes later, the patient developed dyspnea and had an hemoptysis of 50 ml fresh blood. Chest radiograph showed bilateral alveolar infiltrates. Pharyngo-laryngeal examination was normal. Bronchoscopy revealed no injury but diffuse pink frothy edema fluid. Clinical examination and chest radiograph became normal after 12 hr of nasal oxygen therapy confirming airway obstruction as the most available cause of this pulmonary edema. CONCLUSION: Airway obstruction due to biting of a laryngeal mask tube may result in negative pressure pulmonary edema.

Alveolar epithelial fluid transport can be simultaneously upregulated by both KGF and beta-agonist therapy.

Although keratinocyte growth factor (KGF) protects against experimental acute lung injury, the mechanisms for the protective effect are incompletely understood. Therefore, the time-dependent effects of KGF on alveolar epithelial fluid transport were studied in rats 48-240 h after intratracheal administration of KGF (5 mg/kg). There was a marked proliferative response to KGF, measured both by in vivo bromodeoxyuridine staining and by staining with an antibody to a type II cell antigen. In controls, alveolar liquid clearance (ALC) was 23 +/- 3%/h. After KGF pretreatment, ALC was significantly increased to 30 +/- 2%/h at 48 h, to 39 +/- 2%/h at 72 h, and to 36 +/- 3%/h at 120 h compared with controls (P < 0.05). By 240 h, ALC had returned to near-control levels (26 +/- 2%/h). The increase in ALC was explained primarily by the proliferation of alveolar type II cells, since there was a good correlation between the number of alveolar type II cells and the increase in ALC (r = 0.92, P = 0.02). The fraction of ALC inhibited by amiloride was similar in control rats (33%) as in 72-h KGF-pretreated rats (38%), indicating that there was probably no major change in the apical pathways for Na uptake in the KGF-pretreated rats at this time point. However, more rapid ALC at 120 h, compared with 48 h after KGF treatment, may be explained by greater maturation of alpha-epithelial Na channel, since its expression was greater at 120 than at 48 h, whereas the number of type II cells was the same at these two time points. beta-Adrenergic stimulation with terbutaline 72 h after KGF pretreatment further increased ALC to 50 +/- 7%/h (P < 0.5). In summary, KGF induced a sustained increase over 120 h in the fluid transport capacity of the alveolar epithelium. This impressive upregulation in fluid transport was further enhanced with beta-adrenergic agonist therapy, thus providing evidence that two different treatments can simultaneously increase the fluid transport capacity of the alveolar epithelium.

Postoperative hypoxaemia: continuous extradural infusion of bupivacaine and morphine vs patient-controlled analgesia with intravenous morphine.

We carried out a randomized prospective study in 60 patients who had undergone major abdominal surgery for cancer. For postoperative pain control, 30 patients received continuous extradural infusion of 0.125% bupivacaine 12.5 mg h-1 and morphine 0.25 mg h-1 (EXI group) and 30 received patient-controlled analgesia (PCA) with intravenous morphine (1 mg bolus, 5-min lock-out and maximum dose 20 mg 4h-1). Both groups had general anaesthesia. The two groups were compared for postoperative pain scores, satisfaction, sedation and oxygen saturation. Oxygen saturation was recorded continuously the night before surgery and for two consecutive postoperative nights. Episodes of moderate desaturation (90% > SpO2 85%) were more frequent in the EXI group than in the PCA group (P < 0.05). Pain scores were lower in the EXI group compared with the PCA group at rest and while coughing (P < 0.05). No significant difference was found for patient sedation and satisfaction.

[Repercussion of postoperative pain, benefits attending to treatment]. / Retentissements de la douleur postopératoire, bénéfices attendus des traitements.

Physiological responses to postoperative acute pain may impede organ functions (cardiovascular, pulmonary, coagulation, endocrine, gastrointestinal, central nervous system, etc). Pain alleviation improves patient's comfort, but also may minimise perioperative stress response, physiological responses and postoperative organ dysfunction, assist postoperative nursing and physiotherapy, enhance clinical outcome, and potentially shorten the hospital stay. Potent postoperative analgesia, especially by epidural route, may be associated with reduction in incidence and severity of many perioperative dysfunctions. Peridural analgesia using local anaesthetics is the best technique for decreasing postoperative stress after lower abdominal or lower limb surgery. Analgesia using either epidural or high doses of morphine may improve some cardiac variables such as tachycardia and ischaemia, but does not change the incidence of severe cardiac complications. For patients undergoing vascular or orthopaedic surgery, epidural analgesia can improve clinical outcome by preventing the development of arterial or venous thromboembolic complications. However, in comparative studies, the control groups did not receive adequate prophylactic treatment for thromboembolic complications. Epidural analgesia can hasten the return of gastrointestinal motility and shorten the hospital stay. Postoperative mental dysfunction is decreased using intravenous PCA morphine in the elderly. Epidural analgesia with local anaesthetics improves postoperative respiratory function but, for unknown reasons, these benefits are not associated with a decrease in respiratory complications. On balance, the mode of acute pain relief decreases adverse physiological responses and many intermediate outcome variables; however, there is inconclusive evidence that it affects clinical outcome. Major advances in postoperative recovery can be achieved by early aggressive perioperative care, including potent analgesia, early mobilisation and oral nutrition. As a result, the hospital stay may be shortened.

Upregulation of alveolar epithelial fluid transport after subacute lung injury in rats from bleomycin.

Alveolar epithelial fluid transport was studied 10 days after subacute lung injury had been induced with intratracheal bleomycin (0.75 U). An isosmolar Ringer lactate solution with 5% bovine serum albumin and 125I-labeled albumin as the alveolar protein tracer was instilled into the right lung; the rats were then studied for either 1 or 4 h. Alveolar fluid clearance was increased in bleomycin-injured rats by 110% over 1 h and by 75% over 4 h compared with control rats (P < 0.05). The increase in alveolar fluid clearance was partially inhibited by amiloride (10(-3) M). Alveolar fluid clearance decreased toward normal levels in rats that were studied 60 days after bleomycin instillation. Remarkably, the measured increase in net alveolar fluid clearance occurred in the presence of a significant increase in alveolar epithelial permeability to protein. Moreover, the increase in alveolar epithelial fluid clearance occurred even though the mRNA for the alpha-subunit of the epithelial sodium channel was decreased in alveolar epithelial type II cells isolated from these rats. In addition, 22Na uptake by isolated alveolar epithelial type II cells from rats treated with bleomycin demonstrated a 52% decrease in uptake compared with type II cells from control rats. Morphological results demonstrated a significant hyperplasia of alveolar type II epithelial cells 10 days after bleomycin injury. Thus, these results provide evidence that proliferation of alveolar epithelial type II cells after acute lung injury may upregulate the transport capacity of the alveolar epithelium, even though the expression of epithelial sodium channels is reduced and the uptake of 22Na per cell is also reduced. These results may have clinical relevance for the resolution of alveolar edema in the subacute phase of lung injury.

Halothane and isoflurane decrease alveolar epithelial fluid clearance in rats.

BACKGROUND: Active sodium transport is the primary mechanism that drives alveolar fluid clearance. In the current study, the effects of exposure to halothane and isoflurane on alveolar fluid clearance in rats were evaluated. METHODS: Rats were exposed to either halothane (0.4% for 6 h or 2% for 2 h) or isoflurane (0.6% for 6 h or 2.8% for 2 h). Reversibility of halothane effects was assessed after 2 h of exposure to 2% halothane. Alveolar and lung liquid clearance were measured by intratracheal instillation of a 5% albumin solution with 1.5 microCi of 125I-albumin, during mechanical ventilation with 100% FiO2 and the halogenated agent. The effect of terbutaline (10(-4) M) added to the albumin solution was tested after 2 h of exposure to 2% halothane. The increase in protein concentration in the airspaces over 1 h was used to evaluate alveolar liquid clearance. Lung liquid clearance was calculated gravimetrically. RESULTS: Alveolar liquid clearance rates were decreased by 24%, 30% and 40% compared with controls (P < 0.05) after 2 h of exposure to halothane, 6 h of exposure to halothane, and 6 h of exposure to isoflurane, respectively. After 2 h of exposure to isoflurane, alveolar liquid clearance did not change. In the 2-h halothane exposure group, alveolar liquid clearance returned to the control value 2 h after withdrawal of halothane. Terbutaline increased alveolar liquid clearance by 50% and 89% in the control and 2-h halothane exposure groups, respectively. In all experiments, the same results were obtained for alveolar and lung liquid clearance. CONCLUSIONS: Halothane and isoflurane caused a reversible decrease in alveolar epithelial fluid clearance. Two hours of exposure to halothane did not alter the stimulatory effect of terbutaline on alveolar liquid clearance.

Continuous epidural infusion of ropivacaine for postoperative analgesia after major abdominal surgery: comparative study with i.v. PCA morphine.

We have compared the quality of three regimens of postoperative analgesia (continuous epidural administration of ropivacaine (Ropi. group), epidural ropivacaine and patient-controlled analgesia (PCA) with i.v. morphine (Ropi. + PCA group) and PCA morphine alone (PCA group)) during the first postoperative 24 h in a multicentre, randomized, prospective study. Postoperative analgesia was studied in 130 patients after major abdominal surgery performed under general anaesthesia. The ropivacaine groups received 20 ml of epidural bolus ropivacaine 2 mg ml-1 via the epidural route at the end of surgery, followed by continuous infusion of 10 ml h-1 for 24 h. The Ropi. + PCA group also had access to i.v. PCA morphine 1 mg, with a 5-min lockout. The PCA group received morphine as the sole postoperative pain treatment. The two ropivacaine groups had lower pain scores (P < 0.01) than the PCA group. Morphine consumption was higher in the PCA group (P < 0.05) than in the two ropivacaine groups. The quality of pain relief was rated as good or excellent in 79-85% of patients in the three groups. The percentage of patients without motor block increased between 4 and 24 h from 61% to 89% in the Ropi. group, and from 51% to 71% in the Ropi. + PCA group.

Effects of inhaled nitric oxide or inhibition of endogenous nitric oxide formation on hyperoxic lung injury.

Nitric oxide (NO) may either protect against or contribute to oxidant-induced lung injury. In this study, we sought to determine whether either inhaled NO in concentration of 10 and 100 parts per million (ppm) or inhibition of endogenous NO formation with L-NG nitroarginine methyl ester (L-NAME) or aminoguanidine alters the extent of lung injury in rats breathing 100% O2. Lung thiobarbituric acid reactive substances (TBARS), wet to dry lung weight ratio (Q(W)/Q(D)), vascular and epithelial permeability (assessed by simultaneous intravenous administration of 131I-labeled albumin and intraalveolar instillation of 125I-labeled albumin), alveolar liquid clearance (evaluated based on the increase in alveolar protein concentration), and lung liquid clearance (gravimetric method) were determined after 40 h exposure to either 100% or 21% O2. Exposure to hyperoxia caused increases in lung TBARS from 10.5 +/- 0.7 to 13.7 +/- 1.5 micromol/mg protein (p < 0.05); in blood hemoglobin concentration (Hb) from 14 +/- 1 g/dl to 17 +/- 1 g/dl (p < 0.05); in the Q(W)/Q(D) ratio from 4.02 +/- 0.3 to 5.31 +/- 0.5 (p < 0.05); and in alveolar-arterial oxygen tension difference from 124 +/- 14 mm Hg to 241 +/- 61 mm Hg (p < 0.05); as well as a decrease in blood pressure, from 131 +/- 15 mm Hg to 72 +/- 26 mm Hg (p < 0.05). Hyperoxia also increased vascular albumin leakage and moderately altered epithelial barrier permeability to protein. Inhalation of 10 ppm NO prevented the increases in TBARS and Q(W)/Q(D), had no effect on the alveolar barrier impermeability to protein, and improved alveolar liquid clearance. Inhalation of 100 ppm NO did not alter the increases in TBARS and Q(W)/Q(D) but increased vascular permeability to protein. Survival of rats exposed to hyperoxia was not improved by inhaled NO. Treatment with L-NAME or aminoguanidine reduced survival. L-NAME, but not aminoguanidine, increased lung TBARs. These results suggest that, depending on its concentration, inhaled NO can either reduce or increase the early consequences of hyperoxic lung injury. Treatment with L-NAME, and to a lesser extent aminoguanidine, worsened hyperoxic lung injury, indicating a protective effect of endogenous NO.

Alveolar epithelial fluid clearance mechanisms are intact after moderate hyperoxic lung injury in rats.

The capacity of the alveolar epithelial barrier to remove excess alveolar fluid from the airspaces of the lung was studied in an experimental model of moderate hyperoxic lung injury. Rats were exposed to 100% oxygen for 40 h in an exposure chamber and compared with control animals exposed to room air. Extravascular lung water was calculated gravimetrically. Alveolar and lung liquid clearance were studied over 1 h by instillation of a 5% albumin solution with 1.5 microCi of 125I-labeled albumin (6 mL/kg into both lungs). The concentration of both the unlabeled and labeled albumin was used to calculate alveolar liquid clearance. Hyperoxic rats developed pulmonary edema, with a 33% increase in extravascular lung water to 5.3 +/- 0.1 g of water per gram of dry lung, compared with 4.0 +/- 0.2 g of water per gram of dry lung in control rats (p < 0.05). This degree of edema was associated with a significant increase in the alveolar-arterial oxygen difference (241 +/- 61 vs 124 +/- 14 mm Hg in control animals exposed to room air, p < 0.05). Despite this moderate degree of lung injury, alveolar fluid clearance was normal (30 +/- 3%) compared with control rats (33 +/- 6%). Furthermore, the hyperoxic injured rats responded normally to an exogenous beta-adrenergic agonist (terbutaline, 10(-4) mol/L) with a 67% increase in the rate of alveolar liquid clearance (50 +/- 5%). Thus, in the setting of moderate hyperoxic lung injury, the alveolar epithelial barrier is still capable of removing fluid at a normal rate and responding to beta-adrenergic agonist treatment. These experimental results have potential clinical implications for patients with acute lung injury.

Acute bacterial pneumonia in rats increases alveolar epithelial fluid clearance by a tumor necrosis factor-alpha-dependent mechanism.

To study the rate and regulation of alveolar fluid clearance in acute pneumonia, we created a model of Pseudomonas aeruginosa pneumonia in rats. To measure alveolar liquid and protein clearance, we instilled into the airspaces a 5% bovine albumin solution with 1.5 microCi of 125I-human albumin, 24 h after intratracheal instillation of bacteria. The concentration of unlabeled and labeled protein in the distal airspaces over 1 h was used as an index of net alveolar fluid clearance. Since there was histologic evidence of alveolar epithelial injury, several methods were used to measure alveolar fluid clearance, including the use of experiments in rats with blood flow and the use of experiments in rats without blood flow, so that movement across the epithelial barrier would be minimized in the latter group. The results with each method were identical. We found that P. aeruginosa pneumonia increased alveolar liquid clearance over 1 h by 48% in studies with blood flow, and by 43% in rats without blood flow, compared with respective controls (P < 0.05). In both studies, this increase was inhibited with amiloride. However, propranolol had no inhibitory effect, thus ruling out a catecholamine-dependent mechanism to explain the increase in alveolar fluid clearance. An antitumor necrosis factor-alpha neutralizing antibody, instilled into the lung 5 min before bacteria, prevented the increase in alveolar liquid clearance in rats with pneumonia (P < 0.05). Also, TNFalpha (5 microg) instilled in normal rats increased alveolar liquid clearance by 43% over 1 h compared with control rats (P < 0.05). In normal rats instilled with TNFalpha, propranolol had no inhibitory effect. In conclusion, gram-negative pneumonia markedly upregulates net alveolar epithelial fluid clearance, in part by a TNFalpha-dependent mechanism. This finding provides a novel mechanism for the upregulation of alveolar epithelial sodium and fluid transport from the distal airspaces of the lung.

[Prevention of respiratory complications after abdominal surgery]. / Prévention des complications respiratoires après chirurgie abdominale.

Abdominal surgery, especially upper abdominal surgical procedures are known to adversely affect pulmonary function. Pulmonary complications are the most frequent cause of postoperative morbidity and mortality. This review article aimed to analyse the incidence and risk factors for postoperative pulmonary morbidity and their prevention. The most important means for preoperative assessment is the clinical examination; pulmonary function tests (spirometry) are not reliably predictive for postoperative pulmonary complications. Age, type of surgical procedure, smoking and nutritional state have all been identified as potential predictors for postoperative complications. However, usually there is not enough preoperative time available to obtain beneficial effects of stopping smoking and improvement of nutritional state. In patients with COPD, a preoperative multidisciplinary evaluation including the primary care physician, pulmonologist/intensivist, anesthesiologist and surgeon is required. Consensus as to preoperative physiologic state, therapeutic preparation, and postoperative management is essential. Simple spirometry and arterial blood gas analysis are indicated in patients exhibiting symptoms of obstructive airway disease. There are no values that contra-indicate an essential surgical procedure. Smoking should stop at least 8 weeks preoperatively. Preoperative therapy for elective surgery with antibiotics, beta2-agonist, or anticholinergic bronchodilator aerosols, as well as training in cough and lung expansion techniques should begin at least 24 to 48 hours preoperatively. Postoperative therapy should be continued for 3 to 5 days. Usually, anaesthesia is responsible for early complications, whereas surgical procedures are often associated with delayed morbidity. Laparoscopic procedures are recommended, as postoperative morbidity and hospital stay seem reduced in patients without COPD. Regional anaesthesia is given as having less adverse effects on pulmonary function than general anaesthesia. However, for unknown reasons these benefits are not associated with a decrease in postoperative respiratory complications. Moreover, the quality or the type of postoperative analgesia does not influence postoperative respiratory morbidity. Postoperatively, oxygen administration increases SaO2, but cannot abolish desaturation due to obstructive apnea. The various techniques of physiotherapy (chest physiotherapy, incentive spirometry, continuous positive airway pressure breathing) seem to be equivalent in efficacy; but intermittent positive pressure breathing has no advantages, compared with the other treatments and could even be deleterious. Chest physiotherapy and incentive spirometry are the most practical methods available for decreasing secretion contents of airways, whereas continuous positive airway pressure breathing is efficient on atelectasis. In stage II or III COPD patients, admission in a intensive therapy unit and prolonged mechanical ventilation may be required.

Alveolar endotoxin increases alveolar liquid clearance in rats.

Under some pathological conditions, ion transport across alveolar epithelial cells is downregulated, whereas under other pathological conditions, it may be upregulated. Because endotoxin is a biologically relevant pathological stimulus, we investigated the effect of endotoxin on alveolar epithelial liquid clearance in vivo. Escherichia coli endotoxin (220 micrograms/kg) was instilled into the lungs via the trachea of rats. Then, 24 or 40 h after endotoxin instillation, alveolar and lung liquid clearances were studied over 1 h by instillation of a 5% albumin solution with 1.5 microCi of 125I-labeled albumin (6 ml/kg into both lungs). Alveolar liquid clearance was significantly greater at 24 h (36 +/- 5%) and 40 h (38 +/- 7%) after endotoxin exposure than in saline-instilled controls (27 +/- 6%). Although there was an influx of neutrophils into the air space, there was no increase in lung epithelial permeability to protein at 24 or 40 h. Amiloride (2 x 10(-3) M), a sodium channel inhibitor, significantly reduced alveolar liquid clearance in the rats exposed to endotoxin. However, the increase in alveolar liquid clearance was not inhibited when propranolol (2 x 10(-5) M) was added to the 5% albumin solution. Thus exposure to alveolar endotoxin upregulates net alveolar fluid clearance in vivo for up to 40 h, a potentially important mechanism for accelerating alveolar fluid clearance under some pathological conditions. The increase in alveolar liquid clearance 24 and 40 h after instillation of endotoxin into the air spaces is mediated by an increased uptake of sodium through amiloride-sensitive sodium channels.