Introduction Caspofungin treatment is frequently initiated in shock patients. In the present study, we investigated the influence of hypovolaemic shock requiring fluid loading on the plasma and pulmonary pharmacokinetic parameters of caspofungin in the pig. Methods After being anaesthetised and mechanically ventilated, 12 pigs were bled to induce a two-hour deep shock and resuscitated using normal saline based on haemodynamic goals. A one-hour infusion of 70 mg of caspofungin was started at the beginning of the resuscitation period. The lungs were removed four hours after caspofungin administration. Sixteen animals served as controls without haemorrhage. Caspofungin concentrations were measured by using high-performance liquid chromatography, and a two-compartment population pharmacokinetic analysis was performed. Results In the shock group, the volume of blood removed was 39 ± 7 mL/kg and a volume of 90 ± 17 mL/kg saline was infused throughout the resuscitation period. The extravascular lung water index was higher in the shock group (9.3 ± 1.6 mL/kg vs 5.7 ± 1 mL/kg in the control group; P < 0.01). In the shock group, the median (interquartile range) maximal plasma concentration was 37% lower than in the control group (21.6 μg/mL (20.7 to 22.3) vs 33.1 μg/mL (28.1 to 38.3); P < 0.01). The median area under curve (AUC) from zero to four hours was 25% lower in the shock group than in the control group (60.3 hours × μg/mL (58.4 to 66.4) vs 80.8 hours × μg/mL (78.3 to 96.9); P < 0.01), as was the median lung caspofungin concentration (1.22 μg/g (0.89 to 1.46) vs 1.64 μg/g (1.22 to 2.01); P < 0.01). However, the plasma-to-tissue ratios were not different between the groups, indicating that lung diffusion of caspofungin was not affected after shock followed by fluid loading. Pharmacokinetic analysis showed that the peripheral volume of distribution of caspofungin and intercompartmental clearance were significantly higher in the shock group, as was the total apparent volume of distribution. Conclusions Hypovolaemic shock followed by fluid loading in the pig results in a significant increase in the apparent volume of distribution of caspofungin and in a decrease in its plasma and pulmonary exposition. Although our model was associated with capillary leakage and pulmonary oedema, our results should be generalised to the septic shock with caution. Future investigations should focus on monitoring plasma caspofungin concentrations and optimal caspofungin dosing in shock patients.

Background: Respiratory complications are the most frequent concern following oesophagectomy. We aimed to assess the postoperative inflammatory response after oesophagectomy and to determine its reliability to predict the occurrence of pulmonary complications. Methods: A total of 97 patients were enrolled in this prospective observational study. All patients underwent a transthoracic oesophagectomy for cancer. From DO to D3, plasmatic cytokine levels (interleukin (IL)-1, IL-6, IL-8, IL-10, tumour necrosis factor (INF)-alpha), short synacthen test (SST), PaO(2)/FiO(2) ratio and clinical factors determining the systemic inflammatory response syndrome (SIRS) were monitored and compared between patients who experienced pulmonary complications (group I) and those who did not (group II). Results: The overall in-hospital mortality was 5%. Postoperative pulmonary complications occurred in 33 patients (34%). Sputum retention was the first step of pulmonary complications in 26 patients (occurring at a mean of 2.8 +/- 1 days after the operation), leading to pneumonia in 22 patients (4.7 +/- 1 days) and acute respiratory distress syndrome (ARDS) in 10 (6.9 +/- 3 days). At day 2, group I patients had significantly higher plasmatic levels of IL-6, IL-10 and TNF-alpha than group II patients. PaO(2)/FiO(2) was impaired accordingly (215 vs 348; p = 0.006). SST was negative in 38% of group I patients and in 30% of group II patients (p = 0.51). SIRS was present in 33% and 6% of group I and group II patients, respectively (p <= 0.01). At multivariate analysis, early occurrence of SIRS was the sole significant predictor of pulmonary complications (p = 0.005; odds ratio (OR):11.4, confidence interval (CI): 2-63). Conclusions: The vast majority of postoperative pulmonary complications after oesophagectomy occur after the 4th postoperative day. The earlier detection (first 48 h) of SIRS, high plasmatic cytokine levels and impairment of PaO(2)/FiO(2) predicts the onset of these complications. This finding suggests that early pharmacological intervention may have a beneficial impact. (C) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

BACKGROUND:Although a strategy of tidal volume (V(t)) reduction during the one-lung ventilation (OLV) period is advised in thoracic surgery, the influence of the pre-operative respiratory status on the tolerance of this strategy remains unknown. Therefore, the aim of this study was to compare the pulmonary function between chronic obstructive pulmonary disease (COPD) and healthy-lung patients during the operative and the post-operative period.METHODS:Forty-eight patients undergoing a planned lobectomy for cancer and presenting either a healthy lung function (n=24) or a moderate COPD stage (n=24) were ventilated without external positive end-expiratory pressure (PEEP) and received 9 ml/kg V(t) during the two-lung ventilation (TLV) period, secondary reduced to 6 ml/kg during the OLV period. Lung function was assessed by peroperative gas exchange, venous admixture, respiratory mechanical parameters and post-operative spirometric measurements.RESULTS:Although the PaO(2) was superior in the healthy-lung group during the TLV, once the OLV was established, no difference was observed between the two groups. Moreover, the PaO(2)/FiO(2) was proportionally more impaired in the healthy-lung group compared with the COPD group (50 ± 13 vs. 72 ± 19% of the baseline values after exclusion and 32 ± 15 vs. 51 ± 25% after the thoracotomy, P<0.05 for each) as well as the venous admixture. In the post-operative period, a higher decrease was observed in the healthy-lung group for the forced vital capacity and the forced expiratory volume.CONCLUSIONS:Reducing V(t) to 6 ml/kg without the adjunction of external PEEP during OLV is associated with better preservation of lung function in the case of moderate COPD than in the case of healthy-lung status.

MAJOR abdominal and thoracic surgeries are frequently associated with postoperative acute respiratory failure (ARF) as a result of atelectasis or pneumonia.1In the follow-up to this type of surgery, increasing numbers of reports suggest that noninvasive ventilation (NIV) may help prevent ARF.2–4The Case Scenario presented here illustrates the potential benefit of applying NIV. In addition, it highlights the importance of applying a multifaceted postoperative strategy rather than a single therapeutic strategy. This Case Scenario aims to identify key points that can help medical practitioners to make the correct choice as to whether to use NIV or not following invasive surgery.A 63-yr-old man underwent transthoracic esophagectomy for adenocarcinoma; he experienced progressive ARF starting 24 h after surgery. The patient was scheduled for esophagectomy after neoadjuvant radiochemotherapy. His pulmonary function test did not demonstrate any abnormalities, revealing a forced expiratory volume of 3 l per second and a forced vital capacity of 3.43 l, both of which are more than 95% of the predicted value associated with normal gas exchange (table 1). The patient was a former smoker (10 cigarettes a day for at least 15 yr) but had stopped 5 yr before surgery; a moderate alcohol intoxication was noted at the time of surgery. The patient presented a 5 kg weight loss without impairment of nutritional status (serum albumin level of 28 g/l). Neuraxial analgesia was not planned because the patient presented a medical history of coronary disease, having undergone endovascular stent graft placement 2 yr before the intervention described here. This stent graft required continuation of antiplatelet therapy (acetylsalicylic acid). The surgical procedure for esophagectomy lasted 290 min; it included a median laparotomy with creation of a neoesophagus using the stomach, followed by a right thoracotomy with right pulmonary exclusion, with the patient placed in the left decubitus position. This allowed subtotal esophagectomy and esophageal reconstruction through the thoracic route. The patient was put under protective ventilation5throughout the procedure. This included 5 cm H2O positive end-expiratory pressure. During the two-lung ventilation period, tidal volume was 9 ml/kg; this was reduced to 5 ml/kg during the one-lung period (78 min). According to these settings, inspiratory fraction of oxygen levels were maintained at 60% during the whole anesthetic period, and oxygen saturation did not drop below 96%. No difficulties were encountered during either the surgical procedure or the immediate postoperative period. Tracheal extubation was performed before transfer from the operating theater to the intensive care unit. Postoperative analgesia was provided by intravenous acetaminophen (1 g every 6 h) and patient-controlled analgesia associating morphine and ketamine, with a bolus dose of 0.015 mg/kg each every 7 min; the number of doses was not limited. This analgesic strategy was initially associated with a visual analog pain score, which was maintained at less than 40 mm over the first 18 h. Respiratory rehabilitation consisted in twice-daily chest physiotherapy (30 min), incentive spirometry, and early mobilization. Unfortunately, from the end of the first postoperative day, the patient became resistant to physiotherapy and showed progressive sputum retention and moderate hypoxemia. On the second postoperative day, the patient's respiratory status worsened; tachypnea (less than 30 breaths/min), superficial ventilation, and confusion were observed. Moreover, the patient complained of thoracic pain (visual analog pain score higher than 60 mm) and required more pain relief (morphine consumption greater than 15 mg/8 h). Considering the preoperative alcohol intoxication noted, some of these symptoms might be attributed to delirium tremens. Nevertheless, the combination of hypoxemia and cumulative morphine doses explains our concern for these symptoms. Faced with the rapid degradation of the patient's health status and his increasing tachycardia, the potential benefit of neuraxial analgesia was suggested. Given the antiplatelet drug regime, the risk of infection, and a similar benefit in analgesic control, a paravertebral block was deemed preferable to epidural analgesia. Because a paravertebral block does not require epidural puncture, the risk of compressive hematoma is reduced. The paravertebral block infusion (2 mg/ml ropivacaine) started at an initial flow of 6 ml/h; flow was rapidly increased to 10 ml/h. This resulted in vertebral blockade from T6 to T10 and was associated with an improvement in patient compliance with care. A visual analog pain score lower than 40 mm with the paravertebral infusion allowed the patient-controlled analgesia to be stopped. Despite this change in analgesia, the patient's respiratory distress worsened on the third postoperative day with tachypnea greater than 30 breaths/min, active contraction of accessory muscles, temperature above 39°C, macroscopically purulent secretion associated with leukocytosis (white cell count of 16,000/mm3), and hypoxemia requiring increased oxygen supply (table 1). These clinical signs were associated with the radiographic observation of right lower- and middle-lobe infiltrates, suggesting the development of pneumonia. In the immediate postoperative period, a surgical cause for these symptoms must be ruled out. Anastomotic leakage or pleural empyema were excluded because chest drainage discharge was normal and a methylene blue test through the nasogastric tube was negative. Therefore, the patient was treated with noninvasive positive pressure ventilation combined with a first-line antibiotherapy using an association of piperacillin/tazobactam and amikacin. Pressure support was initially set at 8 cm H2O over a positive end-expiratory pressure of 4 cm H2O for periods of 45 min separated by intervals of 60 min. Despite moderate delirium, the association of NIV, paravertebral block, and antibiotherapy led to progressively improved oxygenation, thus eliminating the immediate need for tracheal intubation and invasive mechanical ventilation. The thought process leading to the use of NIV in this case is summarized in table 2.Important issues to consider in this case include the following.1. What Is the Pathophysiology of Respiratory Failure after Esophagectomy?Despite continuous progress in surgical, anesthetic, and intensive care techniques, carcinoma of the esophagus continues to carry a high perioperative mortality rate ranging from 3 to 14% (table 3).1,6–12Death generally results from the development of postoperative respiratory complications.11After esophagectomy, the development of respiratory complications may be explained by two pathologic mechanisms. The first is linked to surgical complications, notably with the occurrence of anastomotic leakage leading to mediastinitis, septic shock, and acute respiratory distress. The second is of medical origin, with multifactorial impairment of respiratory function.Medical causes of respiratory complications can involve muscle dysfunction, alteration of pulmonary mechanics, and development of pulmonary atelectasis, leading to postoperative hypoxemia and inducing the further development of complications such as pneumonia or ARF.13Nevertheless, the frequency and significance of respiratory impairment in cases of thoracic or upper abdominal surgery, and particularly esophagectomy, require specific attention.14Along with the "classic" phenomena which are common after all major surgeries, esophagectomy is also characterized by the association of pre-, peri-, and postoperative pulmonary insult factors (fig. 1). The influence of several preoperative factors, including patient's age, performance status, comorbidity, neoadjuvant chemoradiotherapy, and poor respiratory function have commonly been found to associate with a worse respiratory outcome.10,11,15,16For example, the negative effect of chemoradiotherapy on preoperative pulmonary function and increased postoperative respiratory complications has been demonstrated by an impairment of the lungs' carbon monoxide diffusion capacity.17On the basis of these factors, different preoperative scoring methods have been developed to predict the occurrence of respiratory complications.10,16For instance, Ferguson and Durkin have developed a scoring system using patient age, spirometry results, and performance status to help predict the likelihood of pulmonary and cardiovascular complications after esophagectomy (table 4).10,18However, these preoperative scores underestimate the influence of perioperative events that significantly impact postoperative respiratory outcome. Perioperative management, including the use of a mechanical ventilation strategy, duration of surgical procedure, surgeon's experience, extended lymphadenectomy, and fluid management have all been shown to correlate with the postoperative respiratory status.5,19,20Several reports, including our own observations, demonstrate the influence of one-lung ventilation on the inflammatory process, on respiratory complications, and the importance of a protective respiratory strategy based on the decrease of tidal volume.5During the postoperative period, we suggest the involvement of a "stratified process" or a "multi-hit model" where different factors combine with each other and act synergistically to promote the development of ARF. In this way, the first steps are represented by pre- and perioperative respiratory impairment with reduced residual functional capacity, atelectasis, and related hypoxemia.21This status is aggravated during the first postoperative days if it is associated with persistent diaphragmatic dysfunction, progressive sputum retention, atelectasis, and respiratory muscle exhaustion. Insufficient analgesic management and respiratory rehabilitation could also be factors.8In parallel, and as regularly reported following both thoracic and abdominal surgery, a pulmonary inflammatory response can impair the lung parenchyma, rendering them more sensitive to further aggressions.5,22Unfortunately, after esophagectomy, the inflammatory response is not limited to the lung. Indeed, the physiologic insult resulting from esophagectomy is perhaps one of the most apparent because this surgery involves multiple surgical fields. The operative trauma is known to activate several immune cells, which results in the production of proinflammatory cytokines and promotes the development of a systemic inflammatory response.22Moreover, initiation of a systemic inflammatory response has previously been correlated with the further development of postoperative complications and the onset of organ dysfunction.23,24All of these mechanisms occurring simultaneously probably negatively influence each other, thus resulting in a "vicious circle."Finally, the medical and surgical complications are closely linked in the case of esophagectomy. This specificity is explained by the influence of respiratory distress and inflammation on the anastomotic area. After ARF, the second most severe complication is the occurrence of anastomotic leakage. This is closely linked to ischemia of the gastric conduit25and impaired oxygen delivery,26both of which are observed when respiratory failure occurs in combination with systemic inflammation. It is therefore crucial to maintain adequate oxygenation throughout the postoperative period for both surgical and medical reasons, especially when ARF occurs.11Although postoperative ARF is often characterized by the association of hypoxemia with hypercapnia, in our case, arterial blood gas analysis showed that ARF was characterized mainly by hypoxemia in the absence of hypercapnia. This is in accordance with previously published results.2However, this particularity requires confirmation through further study because of its impact on the management of ARF.2. How Is Postesophagectomy ARF Managed?To deal with the complexity of ARF after esophagectomy, the patient must be treated by a multidisciplinary medical staff. The first step is to establish whether there is any involvement of surgical complications, such as anastomotic leakage, in particular with regard to the potential respiratory consequences.27This hypothesis requires that a surgeon be consulted; chest drainage discharge be examined for abnormalities; a methylene blue test through the nasogastric tube be carried out; computed tomography examinations of the chest be performed to identify mediastinitis or pleural empyema; and, if clinical status implies reintubation, a fibroscopic assessment of anastomotic status must be carried out. Once a surgical cause has been eliminated, the practitioners in charge of the patient need to promote respiratory rehabilitation with optimal analgesic control to ensure correct oxygenation. Our case illustrates this issue, highlighting the advantages of neuraxial postoperative analgesia, which not only limits the use of opioid analgesia, but can also improve respiratory function. For a number of years in cases where respiratory function worsens despite adequate analgesic control, as is the case here, invasive mechanical ventilation was the recommended ventilation strategy. Nevertheless, several studies have shown that respiratory morbidity was largely associated with the need for reintubation and mechanical ventilation, notably through the development of ventilator-associated pneumonia.11,28As a result of these studies, strategies changed, and practitioners chose to avoid endotracheal mechanical ventilation for the treatment of ARF, particularly when oxygenation could be preserved through the use of NIV.3. Is There a Clear Indication for NIV, Taking into Account the Proximal Surgical Anastomosis and Current Recommendations for the Use of NIV when Faced with Pneumonia?A recent review and guidelines have reported the potential interest of NIV in postoperative ARF.29However, only a few prospective randomized studies are available which have demonstrated that NIV reduces the need for invasive mechanical ventilation and the risk of death after solid organ transplantation30and thoracic surgery.4In addition, the clinical benefits of NIV compared with conventional medical treatment in patients with hypoxemic, nonhypercapnic ARF remain to be proven.31This is particularly the case in the setting of esophagectomy, where the balance between potential benefits of NIV and the hypothetical risk of anastomotic leakage must be carefully evaluated.32In the postoperative context, recent results support the safety of NIV in patients with ARF after upper abdominal surgery.2,33We have recently reported a case-control study demonstrating the safety of NIV for patients who developed ARF after esophagectomy and its efficacy in avoiding tracheal intubation.2Furthermore, the same study showed that the use of NIV was not associated with increased anastomotic leakage.2These results corroborated those of previous clinical studies, demonstrating the safety of continuous positive airway pressure (CPAP) after major abdominal surgery.33,34Gastric distension is less problematic with NIV than with CPAP, this might be explained by the fact that inspiratory pressure is limited to less than 25 cm H2O in NIV. At this level, distension is unlikely to occur. In addition, nasogastric drainage is maintained throughout the postoperative period, and this may contribute to the prevention of tracheal acid aspiration.35When considering the use of NIV during the postoperative period, the practitioner must determine when direct reintubation of the patient is preferable to starting NIV and when NIV should be stopped. When dealing with ARF, NIV should not be initiated in patients who are confused, in those unable to cooperate, or in patients presenting hemodynamic instability. Moreover, tracheal intubation should be performed immediately if the ARF worsens despite the correct use of NIV. This is particularly important because delayed reintubation may result in increased mortality.36After 1 day of intensive NIV with periods of up to 2–3 h, the patient's clinical evolution was marked by a progressive deterioration of his condition. Although the capnia was maintained in a normal range, hypoxemia reappeared as soon as the NIV was suspended for a few hours (table 1). A follow-up chest x-ray highlighted this degradation, showing a spread of pneumonia to both lungs. Analysis of the potential causes of this adverse evolution revealed that there were air leaks from the nasobuccal interface, in particular around the exit of the nasogastric tube. These affected patient-ventilator synchrony. To reduce this problem a full facemask was used in place of the nasobuccal mask (fig. 2) and the pressure-support ventilation (Puritan Bennett 840; TYCO, Carlsbad, CA) settings were also modified in order to reduce air leaks. These changes included time-cycling instead of flow-cycling the inspiratory phase and reduction of the assisted inspiratory pressure. After these modifications, patient-ventilator synchrony was improved, and the patient was able to sleep with his new interface for a few hours during the night. Over the subsequent days, the patient was progressively weaned off NIV, and he was discharged from the intensive care unit after 7 days. During the second postoperative week, fibroscopic control of the anastomosis did not reveal any leakage.4. Should NIV in This Setting Be Used Prophylactically Immediately after the Surgical Procedure or Only when ARF Is Diagnosed?Another issue to contend with when considering the use of NIV in the postoperative period is the optimal time for implementation: faced with an established ARF (curative use) or by default immediately after the surgical procedure (prophylactic use). With regard to the clinical course of our patient, one could argue that preventive, rather than curative, application of NIV might have avoided the development of respiratory distress. Although the definitive response remains unknown, some data are currently available for evaluation. One of the first well conducted studies of to the use of NIV during the postoperative period was carried out in the context of patient acute respiratory insufficiency after lung resection (curative use).4This study revealed a reduction in the need for endotracheal mechanical ventilation and in postoperative mortality.4Other papers have confirmed that curative NIV is of benefit in other thoracic or abdominal surgical procedures.2,30On the other hand, Squadrone et al. 3have proposed the use of CPAP for the treatment of moderate hypoxemia at an earlier stage in the postoperative course after major abdominal surgery; this would constitute a preventive use. Consequently, although both strategies appear to give positive results, further studies are required to confirm the clinical benefits acquired through application of NIV earlier in the postoperative course.5. What Are the Optimal Settings for NIV in This Situation?The first and, perhaps the most comfortable, mode of NIV is CPAP. Although CPAP does not correspond to true ventilation, this technique could be easily and rapidly started postoperatively. This would help prevent airway and alveolar collapse and would contribute to the maintenance of functional residual lung capacity, which would lead to an increase in oxygenation. The combination of positive inspiratory pressure support ventilation with CPAP could enhance the efficacy of NIV in improving the "pump" function with a decrease of work for the breathing apparatus. Nevertheless, to maintain patient comfort and interface acceptance, the initiation of NIV should be carried out with both moderate levels of inspiratory pressure support ventilation and positive end-expiratory pressure (which is called CPAP when used alone). In the present case, the initial inspiratory pressure support ventilation was set at 10 cm H2O. This value (potential felt as high by the patient during NIV initiation) probably contributed to the patient's discomfort and to the air leaks detected around the interface. The choice of interface is very important when applying NIV, and even more so when a gastric tube is present, as in the case described here. Consequently, and because there is no evidence to support the use of a particular interface in the surgical context, the physician in charge of the patient must try out several interfaces to find that which ensures minimal leaks.We have reported the fact that in our case, arterial blood gas analysis showed that ARF was characterized mainly by hypoxemia without hypercapnia, in accordance with previous results.2Consequently, the settings of NIV should be based on the preferential use of positive end-expiratory pressure rather than inspiratory pressure assist ventilation, as previously used by Squadrone et al. 3Nevertheless, whether the use of positive end-expiratory pressure alone will prevent further muscle exhaustion remains to be answered.6. How Can the Analgesic Strategy Influence Patient Tolerance when Faced with Complications and Related Therapeutic Measures?Patient compliance with treatment is mandatory for NIV to be effective. This can be notably enhanced by providing preoperative information, by ensuring interface acceptance, by adapting and progressively increasing pressure settings, and, not least, by skilled staff.31,33,37Within the context of postoperative respiratory rehabilitation, NIV use also needs a "positive atmosphere" to be optimal. Because of this, and particularly in the postesophagectomy situation, analgesic control appears of paramount importance. The case reported here clearly demonstrated that insufficient analgesic control could contribute to a loss of patient compliance and subsequent impairment of respiratory function. The use of neuraxial analgesia is associated with better relief of pain and fewer opioid-related side effects.8,38This results in a reduction in the need for postoperative ventilation.39Furthermore, Rigg et al. 40have reported a positive influence of epidural analgesia on the outcome of major abdominal surgery. After esophagectomy, specific effects of analgesic strategies should be highlighted. We have reported the benefit of epidural analgesia on the improvement of anastomotic perfusion.27,41This could partly explain the protective influence of this technique after esophagectomy. Unfortunately, epidural analgesia could not be used in the case described here because of the patient's antiplatelet therapy. Although we could retrospectively regret not having applied neuraxial analgesia for this patient in the immediate postoperative period, the balance between benefits and potential risks was considered to weigh against the placement of this technique by the physician in charge of the patient at that time. While the published literature remains insufficient, several studies have already highlighted the potential beneficial effects of a paravertebral block.42Taken together, all of these factors explain why we are so interested in the association of neuraxial analgesia with NIV. Indeed, this association probably results in a synergistic effect for both curative and preventive applications. Once pain is under control, patient compliance may be reinforced by the use of the best-adapted interface, that which provides the best match between the human and the "machine."31,37Clinical studies are mandatory to confirm that NIV is relevant in the specific situation of esophagectomy. It is particularly important to determine the optimal time for introduction of the technique. Indeed, although data are still insufficient to conclude, a recent study supports the initiation of NIV before a thoracic procedure to optimize respiratory function at a very early stage.43Further research will also provide information concerning better (earlier) preservation of the respiratory function and control of the postoperative inflammatory reaction. In the case presented here, we have discussed how NIV and analgesic control can combine to contribute to patient comfort and well-being, but these techniques are currently employed more to correct an existing respiratory impairment. How the implementation of these two techniques could prevent the development of such abnormalities represents an interesting issue for the future.An extensive analysis of the involvement of the abdominal muscles in postoperative respiratory dysfunction is also required.44This should be coupled to the development of analgesic techniques providing better abdominal recovery.45Similarly, it will also be necessary to study the specific influence of NIV on abdominal muscle dysfunction.We have repeatedly mentioned the inflammatory response as one of the main factors influencing respiratory impairment. This aspect is probably highly significant, particularly when one considers the potential influence of postoperative respiratory complications and related immune abnormalities on cancer recurrence and long-term survival.17,46Therefore, for esophagectomy patients, one of the main knowledge gaps is how the immune response can be modulated without completely suppressing its capacity. How is the inflammatory response affected by the use of NIV, of different analgesic strategies, and of combinations of the two?Finally, we have mentioned numerous factors potentially involved in the initiation of respiratory complications. These factors can either protect against, or aggressively influence, respiratory complications. Further studies would provide the physician with new predictive scores to evaluate not only pre- but also peri- and postoperative factors.The authors thank Maighread Gallagher, Ph.D. (TWS Editing, St. Egreve, France), for reviewing the manuscript.

Pulmonary hypertension is defined by a mean pulmonary arterial pressure above 25 mmHg at rest.It may be encountered in the intensive care unit in patients with critical illnesses such as acute respiratory distress syndrome, left ventricular dysfunction, and pulmonary embolism, as well as following cardiothoracic surgery. It encompasses a spectrum of pathologies best characterized by their anatomical location : pre capillary arteries and arterioles, alveoli and capillary beds, and post capillary pulmonary veins and venules. Physiopathology is explained by alteration of the synthesis of nitric oxide, prostacyclin, and endothelin-1. This can produce all imbalance between vasodilation and vasoconstriction, and between apoptosis and proliferation. Although new therapies for Pulmonary hypertension have emerged in recent years, the management of critically ill patients with hemodynamically significant pulmonary hypertension remains challenging with the occurrence of right ventricular dysfunction following acute or chronic pressure overload.Hemodynamic goals in patients with right ventricular failure due to pulmonary hypertension are to reduce pulmonary vascular resistances (PVR), increase cardiac Output, optimize Volume and resolve systemic hypotension while avoiding tachyarrhythmia. But symptomatic treatment of pulmonary hypertension must be systematically associated with identification and treatment of the underlying cause. (C) 2009 Elsevier Masson SAS. All rights reserved.

Background: Hypertonic saline may be administered in the setting of lung transplantation but may affect the development of ischemia-reperfusion lung injury. This study investigated the effects of the pre-treatment by intravenous hypertonic saline in a pig model of single lung ischemia-reperfusion.Methods: Forty-three pigs (34 +/- 4 kg) under mechanical ventilation were randomly assigned to a left lung ischemia-reperfusion alone or preceded by 4-ml/kg 7.5% hypertonic saline, 33-ml/kg normal saline, or by the infusion of the vasodilator nicardipine. Animals without ischemia served as controls. After euthanasia, the left lung was sampled for histologic analysis and measurement of lung water and alveolar-capillary permeability.Results: Ischemia-reperfusion resulted in high-permeability pulmonary edema, hypoxemia, and increased interleukin-6 serum level. Hypertonic saline pre-treatment worsened pulmonary edema of the left lung (6.6 +/- 0.7 vs 4.8 +/- 0.8 ml/kg of body weight, p < 0.05) and resulted in a higher ratio of the protein level in the alveolar fluid to the serum protein level (0.41 +/- 0.04 vs 0.21 +/- 0.09, p < 0.05) and in a higher histologic damage score (11 [range, 9-11.75] vs 6.5 [range, 4.5-7.5], p < 0.05) without promoting pulmonary or systemic inflammation. Lung injury was affected neither by normal saline nor by nicardipine pre-treatment. Nicardipine did not influence the deleterious effect of hypertonic saline.Conclusions: Pre-treatment by intravenous hypertonic saline worsened ischemia-reperfusion lung injury independently of its effects on the cardiac index or pulmonary circulation but probably through a direct effect of hyperosmolarity on endothelial permeability.

Les complications respiratoires sont la principale cause de complication médicale après chirurgie de résection de l’œsophage. Les facteurs favorisant leur développement sont présents dès la période préopératoire et doivent être dépistés. La stratégie de ventilation mécanique durant la procédure chirurgicale est désormais reconnue comme un facteur de risque indépendant. Des données préliminaires indiquent qu’une amélioration de la fonction respiratoire pourrait être obtenue par l’emploi de stratégies basées sur la réduction du volume courant et l’adjonction d’une PEP durant la période de ventilation monopulmonaire. Les thérapeutiques utilisées lors de la survenue des complications respiratoires comprennent le maintien d’une analgésie optimale, d’une kinésithérapie active et l’emploi de la ventilation non invasive sans risque de désunion anastomotique. L’intrication des complications médicales et chirurgicales doit constamment faire rechercher une désunion anastomotique lors d’une détresse respiratoire.

To compare lung injury induced by a hemorrhagic shock resuscitated with normal saline or with small volumes of a hypertonic/hyperoncotic solution.

Background: The oesophagectomy procedure includes the formation of a gastric tube to re-establish the continuity of the gastrointestinal tract. The effect of thoracic epidural analgesia (TEA) on gastric mucosal blood flow (GMBF) remains unknown in clinical practice. The aim of this prospective observational study was to assess the microcirculatory changes induced by TEA in the early post-operative course.Methods: Eighteen consecutive patients who underwent radical oesophagectomy with en-bloc resection and two-field lymphadenectomy for oesophageal cancer, and benefited from TEA during the post-operative course, were studied prospectively, and compared with nine patients who declined the use of TEA in the same period (control group). GMBF was measured using a laser Doppler flowmeter in three consecutive time periods (before and after 1 and 18 h of TEA infusion). Post-operative monitoring also included the measurement of arterial pressure, cardiac output, gas exchange and intrathoracic blood volume index.Results: After the first and 18th hour of infusion, TEA induced an increase in GMBF compared with baseline and the control group. The mean arterial pressure and intrathoracic blood volume index decreased after the first hour of TEA infusion with no influence on the cardiac index.Conclusions: This clinical study demonstrates that TEA improves the microcirculation of the gastric tube in the early post-oesophagectomy period. The clinical relevance of TEA in this setting should be validated in larger studies focusing on the clinical outcome following oesophagectomy.

BACKGROUND I.V. patient-controlled analgesia (PCA) with morphine is often used for postoperative analgesia after thoracic surgery, but the required doses may increase postoperative respiratory disorders. Adjunction of ketamine could reduce both doses and related respiratory side-effects. METHODS The main objective of this prospective, randomized double-blinded study was to evaluate the influence of adding ketamine to PCA on morphine consumption and postoperative respiratory disorders. Consecutive patients undergoing lobectomy (n = 50) were randomly assigned to receive, during the postoperative period, either i.v. morphine 1 mg ml(-1) or morphine with ketamine 1 mg ml(-1) for each. Morphine consumption was evaluated by cumulative doses every 12 h for the three postoperative days. Postoperative respiratory disorders were assessed by spirometric evaluation and recording of nocturnal desaturation. RESULTS The adjunction of ketamine resulted in a significant reduction in cumulative morphine consumption as early as the 36th postoperative hour [43 (SD 18) vs 32 (14) mg, P = 0.03] with a similar visual analogue scale. In the morphine group, the percentage of time with desaturation < 90% was higher during the three nights [1.80 (0.21-6.37) vs 0.02 (0-0.13), P < 0.001; 2.15 (0.35-8.65) vs 0.50 (0.01-1.30), P = 0.02; 2.46 (0.57-5.51) vs 0.55 (0.21-1.00), P = 0.02]. The decrease in forced expiratory volume in 1 s was less marked in the ketamine group at the first postoperative day [1.04 (0.68-1.22) litre vs 1.21 (1.10-0.70) litre, P = 0.039]. CONCLUSIONS Adding small doses of ketamine to morphine in PCA devices decreases the morphine consumption and may improve respiratory disorders after thoracic surgery.

STUDY OBJECTIVES:The measurement of extravascular lung water index by double indicator (EVLWIdi) or the measurement of extravascular lung water index by transpulmonary thermodilution (EVLWItt) could be useful after pneumonectomy. Since pulmonary blood flow and volume are altered after pneumonectomy, the validity of these methods is uncertain. This study has compared measurements of EVLWIdi and EVLWItt with measurement of extravascular lung water index by gravimetry (EVLWIg) in a porcine model of pulmonary edema induced after right pneumonectomy.DESIGN:Randomized laboratory study.SETTING:Animal research laboratory.SUBJECTS:Twenty-seven female pigs; mean weight, 35 +/- 5 kg (+/- SD).INTERVENTIONS:The pigs were anesthetized, placed on mechanical ventilation, and allocated to a two-lung group (n = 10) or a right pneumonectomy group (n = 17). EVLWIdi and EVLWItt were measured at baseline, 60 min after pneumonectomy, and 60 min after IV injection of oleic acid (OA).MEASUREMENTS AND RESULTS:There was a good correlation between EVLWIg and EVLWIdi values (r = 0.96, p < 0.0001 in the two-lung group; and r = 0.81, p = 0.02 in the pneumonectomy group). EVLWIdi underestimated EVLWIg in the two-lung group (- 3 mL/kg; 95% confidence interval [CI], - 7 to + 2 mL/kg) and in the pneumonectomy group (- 0.9 mL/kg; 95% CI, - 3.3 to + 1.5 mL/kg). After pneumonectomy, EVLWItt decreased in mean by 27% and increased in mean by 70% after OA acid. There was a good correlation between EVLWIg and EVLWItt values (r = 0.96, p < 0.0001 in the two-lung group; and r = 0.90, p < 0.0001 after pneumonectomy). EVLWItt slightly overestimated gravimetric value in the two-lung group (+ 1.5 mL/kg; 95% CI, - 1.5 to + 4.2 mL/kg) and largely overestimated gravimetric value after pneumonectomy (+ 5 mL/kg; 95% CI, + 3.4 to + 6.8 mL/kg).CONCLUSION:Double-indicator and transpulmonary thermodilution methods could be useful in monitoring extravascular lung water index (EVLWI) after pneumonectomy, but transpulmonary thermodilution largely overestimates EVLWI.

A sixty-year-old woman was admitted in the ICU after Depamide (Valpromide) self-poisoning (430 mg/kg). Four hours after the ingestion, the patient presented coma (Glagow coma score of 3) with bilateral mydriasis requiring tracheal intubation and mechanical ventilation, hypotension requiring epinephrine infusion (0.9 microg/kg per minute), acidosis and hyperlactatemia (29.7 mmol/l at 12 hours) without any kidney or liver failure. The maximal serum valproic acid concentration measured was 342 mg/l after twelve hours (therapeutic rate: 35-85 mg/l). A continuous infusion of sodium bicarbonate was associated with continuous venovenous haemodiafiltration. Progressive haemodynamic improvement and neurologic recovery leaded to extubation at 36 hours.

A sixty-year-old woman was admitted in the ICU after Depamide(R) (Valpromide) self-poisoning (430 mg/kg). Four hours after the ingestion. the patient presented coma (Glagow coma score of 3) with bilateral mydriasis requiring tracheal intubation and mechanical ventilation. hypotension requiring epinephrine infusion (0.9 mug/kg per minute), acidosis and hyperlactatemia (29.7 mmol/l at 12 hours) without any kidney or liver failure. The maximal serum valproic acid concentration measured was 342 mg/l after twelve hours (therapeutic rate: 35-85 mg/l). A continuous infusion of sodium bicarbonate was associated with continuous venovenous haemodiafiltration. Progressive haemodynamic improvement and neurologic recovery leaded to extubation at 36 hours. (C) 2004 Elsevier SAS.

Summary The pulmonary complications represent the first cause of medical complications after esophagectomy. The risk factors implicated in the pulmonary complications development include preoperative factors that must be detected. The ventilatory strategy and especially the tidal volume used during the surgical procedure have been reported as an independent factor for further pulmonary complications after thoracic surgery. Preliminary results demonstrate that the use of reduced tidal volume and moderate PEEP during the one-lung ventilation period are able to preserve the lung function. The therapeutics used in case of pulmonary complications include an optimal analgesics control, an intensive physiotherapy and the non-invasive

Summary The pulmonary complications represent the first cause of medical complications after esophagectomy. The risk factors implicated in the pulmonary complications development include preoperative factors that must be detected. The ventilatory strategy and especially the tidal volume used during the surgical procedure have been reported as an independent factor for further pulmonary complications after thoracic surgery. Preliminary results demonstrate that the use of reduced tidal volume and moderate PEEP during the one-lung ventilation period are able to preserve the lung function. The therapeutics used in case of pulmonary complica- tions include an optimal analgesics control, an intensive physiotherapy and the non-invasive