Physiologic Effects of ECMO in Patients with Severe Acute Respiratory Distress Syndrome.

RATIONALE: Blood flow rate affects mixed venous oxygenation (SvO2) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. OBJECTIVES: We aimed at describing the physiologic effects of different levels of SvO2 obtained by changing ECMO blood flow, in patients with severe ARDS receiving ECMO and controlled mechanical ventilation. METHODS: Low (SvO2 target 70-75%), intermediate (SvO2 target 75-80%) and high (SvO2 target > 80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography (EIT). MEASUREMENTS AND MAIN RESULTS: Cardiac output decreased from low to intermediate and to high blood flow/SvO2 (9.2 [6.2-10.9] vs 8.3 [5.9-9.8] vs 7.9 [6.5-9.1] L/min, p = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs 31 ± 6 vs 30 ± 5 mmHg, p < 0.001), and right ventricle stroke work index (14.2 ± 4.4 vs 12.2 ± 3.6 vs 11.4 ± 3.2 g*m/beat/m2, p = 0.002). Cardiac output was inversely correlated with mixed venous and arterial PO2 values (R2 = 0.257, p = 0.031 and R2 = 0.324, p = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous PO2 (R2 = 0.29, p <0.001) and with increasing cardiac output (R2 = 0.378 p < 0.007). Measures of ventilation/perfusion mismatch did not differ between the three steps. CONCLUSIONS: In severe ARDS patients, increased ECMO blood flow rate resulting in higher SvO2 decreases pulmonary artery pressure, cardiac output, and right heart workload. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Hyperammonemia Syndrome After Lung Transplantation: A Double-Hit Fatal Syndrome. A Case Report.

Hyperammonemia after lung transplantation is a rare but potentially fatal condition. A 59-year-old male patient affected by pulmonary fibrosis underwent an uncomplicated bilateral lung transplant. Fourteen days after the procedure, the patient developed severe encephalopathy caused by elevated serum ammonia levels. Ureaplasma parvum and Mycoplasma hominis were found on bronchial aspirate and urinary samples as well as on pharyngeal and rectal swabs. Despite the initiation of multimodal therapy, brain damage due to hyperosmolarity was so extensive to evolve into brain death. The autopsy revealed glutamine synthetase hypo-expression in the hepatic tissue. The pathophysiology of hyperammonemia syndrome in lung transplant recipients remains unclear. Previous studies have described the presence of disorders of glutamine synthetase, while others considered the infection with urea-splitting microorganisms as a cause of hyperammonemia syndrome. Our report describes the case of a patient who developed hyperammonemia after a lung transplant in which both the aforementioned etiologies were documented. A high level of clinical suspicion for hyperammonemia syndrome should be maintained in lung transplant recipients. Timely recognition and treatment are critical to prevent the potentially dreadful evolution of this severe complication.

Effects of an asymmetrical high flow nasal cannula interface in hypoxemic patients.

BACKGROUND: Optimal noninvasive respiratory support for patients with hypoxemic respiratory failure should minimize work of breathing without increasing the transpulmonary pressure. Recently, an asymmetrical high flow nasal cannula (HFNC) interface (Duet, Fisher & Paykel Healthcare Ltd), in which the caliber of each nasal prong is different, was approved for clinical use. This system might reduce work of breathing by lowering minute ventilation and improving respiratory mechanics. METHODS: We enrolled 10 patients ≥ 18 years of age who were admitted to the Ospedale Maggiore Policlinico ICU in Milan, Italy, and had a PaO2/FiO2 < 300 mmHg during HFNC support with a conventional cannula. We investigated whether the asymmetrical interface, compared to a conventional high flow nasal cannula, reduces minute ventilation and work of breathing. Each patient underwent support with the asymmetrical interface and the conventional interface, applied in a randomized sequence. Each interface was provided at a flow rate of 40 l/min followed by 60 l/min. Patients were continuously monitored with esophageal manometry and electrical impedance tomography. RESULTS: Application of the asymmetrical interface resulted in a -13.5 [-19.4 to (-4.5)] % change in minute ventilation at a flow rate of 40 l/min, p = 0.006 and a -19.6 [-28.0 to (-7.5)] % change at 60 l/min, p = 0.002, that occurred despite no change in PaCO2 (35 [33-42] versus 35 [33-43] mmHg at 40 l/min and 35 [32-41] versus 36 [32-43] mmHg at 60 l/min). Correspondingly, the asymmetrical interface lowered the inspiratory esophageal pressure-time product from 163 [118-210] to 140 [84-159] (cmH2O*s)/min at a flow rate of 40 l/min, p = 0.02 and from 142 [123-178] to 117 [90-137] (cmH2O*s)/min at a flow rate of 60 l/min, p = 0.04. The asymmetrical cannula did not have any impact on oxygenation, the dorsal fraction of ventilation, dynamic lung compliance, or end-expiratory lung impedance, suggesting no major effect on PEEP, lung mechanics, or alveolar recruitment. CONCLUSIONS: An asymmetrical HFNC interface reduces minute ventilation and work of breathing in patients with mild-to-moderate hypoxemic respiratory failure supported with a conventional interface. This appears to be primarily driven by increased ventilatory efficiency due to enhanced CO2 clearance from the upper airway.

Lung Transplant for ARDS after COVID-19: Long-Term Outcomes and Considerations about Detrimental Issues.

During the first outbreak of COVID-19 in Italy, based on the only few cases reported from a Chinese centre at the time, we performed lung transplantation in two patients with irreversible acute respiratory distress syndrome (ARDS) after COVID-19 at our centre. After two years, we report the outcomes of these cases and some considerations. The first patient, an 18-year-old male, is in excellent conditions twenty-four months after surgery. The second patient was a 48-year-old man; his airways were colonized by carbapenemase-producing klebsiella pneumoniae at the time of lung transplantation, and he had previously suffered from delirium and hallucinations in the intensive care unit. His postoperative clinical course was complicated by dysexecutive behaviour and then septic shock; he died 62 days after surgery. The recently reported experience of different transplantation centres has led to the inclusion of irreversible acute respiratory distress syndrome (ARDS) after COVID-19 among the indications for lung transplantation in carefully selected patients. Our results confirm the feasibility and the good long-term outcomes of lung transplantation for COVID-19-associated ARDS. Nonetheless, our experience corroborates the need for careful recipient selection: special attention must be paid to the single-organ dysfunction principle, the evaluation of any neuro-psychiatric disorder, and MDR germs colonization, before listing.

Physiotherapy approach after lung transplantation in a critically ill COVID-19 patient: a case report.

This study describes the case of an 18-years-old male affected by severe COVID-19, who was receiving bilateral lung transplantation (LT), after 71 days of mechanical ventilation and 55 days of veno-venous extracorporeal membrane oxygenation. From post-operative day 2, early mobilization and physiotherapy treatments were performed. Weaning from mechanical ventilation, the use of non-invasive ventilation and tracheostomy management were included in the treatment. Forty-five days after LT the patient was discharged at home, showing improvements in terms of functional and respiratory parameters, quality of life and mood. While evidences about physiotherapy treatments in lung transplantation post severe COVID-19 remain limited, early approach and a multidisciplinary team may be considered key elements for functional recovery of these subjects.

Heparin-Free Lung Transplantation on Venovenous Extracorporeal Membrane Oxygenation Bridge.

Extracorporeal membrane oxygenation (ECMO) bridge to lung transplantation (LuTX) exposes the patients to a high risk of perioperative bleeding secondary to systemic anticoagulation and coagulation factors deficiency. With this case series, we propose innovative "no-heparin" management of ECMO-bridge support during LuTX, based upon 1) control heparin resistance with antithrombin III in the preoperative period; 2) relying upon a fully functional, brand new heparinized ECMO circuit; 3) completely avoiding perioperative heparin; 4) hampering fibrinolysis with tranexamic acid; and 5) limiting venoarterial (VA) ECMO escalation, and the following need for full anticoagulation. Following the application of this new approach, we carried out three challenging clinical cases of bilateral ECMO-bridged LuTX effectively, with limited intraoperative blood requirement and no major postoperative bleeding or thromboembolic events. Of note, two of them had an extremely high risk for hemorrhage due to complete right lung anatomic derangement in case number 2 and surgical adhesion following first LuTX in case number 3, while for the case number 1, no blood products were administered during surgery. Despite the limited patient population, such an approach relies on a strong rationale and may be beneficial for managing ECMO bridging to LuTX. Prospective studies are necessary to confirm the validity of our strategy.

Concurrent Thoracic Endovascular Aortic Repair and Liver Transplant: Multidisciplinary Management of Multiple Posttraumatic Lesions.

Association of thoracic and abdominal injuries in patients with major trauma is common. Under emergency conditions, it is often difficult to promptly perform a certain diagnosis and identify treatment priorities of life-threatening lesions. We present the case of a young man with combined thoracic and abdominal injuries after a motorcycle accident. Primary evaluation through echography and X-ray showed fluid within the hepatorenal recess and an enlarged mediastinum. Volume load, blood transfusions, and vasoactive agents were initiated to sustain circulation. Despite hemodynamic instability, we decided to perform computed tomographic angiography (CTA) scan that revealed a high-grade traumatic aortic pseudoaneurysm, multiple and severe areas of liver contusion, and a small amount of hemoperitoneum, without active bleeding spots. The patient was successfully submitted to thoracic endovascular aortic repair (TEVAR). Immediately after the end of the successful TEVAR, signs of massive abdominal bleeding revealed. Immediate explorative laparotomy was performed showing massive hepatic hemorrhage. After liver packing and Pringle's maneuver, control of bleeding was lastly obtained with hemostatic devices and selective cross-clamping of the right hepatic artery. The patient was then transferred to intensive care unit where, despite absence of further hemorrhage, hemodynamic instability, anuria, severe lactic acidosis together with liver necrosis indices appeared. A new CTA demonstrated massive parenchymal disruption within the right lobe of the liver and multiple hematomas in the left lobe. Considering the high-grade lesions of the hepatic vascular tree and liver failure, patient was listed for emergency liver transplantation (LT). LT occurred few hours later, and patient's clinical conditions rapidly improved even if the subsequent clinical course was characterized by a severe fungal infection because of immunosuppression. Evaluation of life-threatening lesions and treatment priorities, availability of different excellence skills, and multidisciplinary collaboration have a key role to achieve clinical success in such severe cases.

Potential for Lung Recruitment and Ventilation-Perfusion Mismatch in Patients With the Acute Respiratory Distress Syndrome From Coronavirus Disease 2019.

OBJECTIVES: Severe cases of coronavirus disease 2019 develop the acute respiratory distress syndrome, requiring admission to the ICU. This study aimed to describe specific pathophysiological characteristics of acute respiratory distress syndrome from coronavirus disease 2019. DESIGN: Prospective crossover physiologic study. SETTING: ICU of a university-affiliated hospital from northern Italy dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019. PATIENTS: Ten intubated patients with acute respiratory distress syndrome and confirmed diagnosis of coronavirus disease 2019. INTERVENTIONS: We performed a two-step positive end-expiratory pressure trial with change of 10 cm H2O in random order. MEASUREMENTS AND MAIN RESULTS: At each positive end-expiratory pressure level, we assessed arterial blood gases, respiratory mechanics, ventilation inhomogeneity, and potential for lung recruitment by electrical impedance tomography. Potential for lung recruitment was assessed by the recently described recruitment to inflation ratio. In a subgroup of seven paralyzed patients, we also measured ventilation-perfusion mismatch at lower positive end-expiratory pressure by electrical impedance tomography. At higher positive end-expiratory pressure, respiratory mechanics did not change significantly: compliance remained relatively high with low driving pressure. Oxygenation and ventilation inhomogeneity improved but arterial CO2 increased despite unchanged respiratory rate and tidal volume. The recruitment to inflation ratio presented median value higher than previously reported in acute respiratory distress syndrome patients but with large variability (median, 0.79 [0.53-1.08]; range, 0.16-1.40). The FIO2 needed to obtain viable oxygenation at lower positive end-expiratory pressure was significantly correlated with the recruitment to inflation ratio (r = 0.603; p = 0.05). The ventilation-perfusion mismatch was elevated (median, 34% [32-45%] of lung units) and, in six out of seven patients, ventilated nonperfused units represented a much larger proportion than perfused nonventilated ones. CONCLUSIONS: In patients with acute respiratory distress syndrome from coronavirus disease 2019, potential for lung recruitment presents large variability, while elevated dead space fraction may be a specific pathophysiological trait. These findings may guide selection of personalized mechanical ventilation settings.

Spontaneous Breathing Patterns During Maximum Extracorporeal CO2 Removal in Subjects With Early Severe ARDS.

BACKGROUND: Switching patients affected by early severe ARDS and undergoing extracorporeal membrane oxygenation (ECMO) from controlled ventilation to spontaneous breathing can be either beneficial or harmful, depending on how effectively the breathing pattern is controlled with ECMO. Identifying the factors associated with ineffective control of spontaneous breathing with ECMO may advance our pathophysiologic understanding of this syndrome. METHODS: We conducted a prospective study in subjects with severe ARDS who were on ECMO support ≤ 7 d. Subjects were switched to minimal sedation and pressure-support ventilation while extracorporeal CO2 removal was increased to approximate the subject's total CO2 production ([Formula: see text]). We calculated the rapid shallow breathing index (RSBI) as breathing frequency divided by tidal volume. We explored the correlation between certain characteristics recorded during pretest controlled ventilation and the development of apnea (ie, expiratory pause lasting > 10 s; n = 3), normal breathing pattern (ie, apnea to RSBI ≤ 105 breaths/min/L; n = 6), and rapid shallow breathing (RSBI > 105 breaths/min/L; n = 6) that occurred during the test study. RESULTS: The ratio of extracorporeal CO2 removal to the subjects' [Formula: see text] was >90% in all 15 subjects, and arterial blood gases remained within normal ranges. Baseline pretest Sequential Organ Failure Assessment score, total [Formula: see text] and ventilatory ratio increased steadily, whereas [Formula: see text]/[Formula: see text] was higher in subjects with apnea compared to intermediate RSBI ≤105 breaths/min/L and elevated RSBI >105 breaths/min/L. In subjects with rapid shallow breathing, baseline lung weight measured with quantitative computed tomography scored higher, as well. CONCLUSIONS: In early severe ARDS, the factors associated with rapid shallow breathing despite maximum extracorporeal CO2 extraction include less efficient CO2 and O2 exchange by the natural lung, higher severity of organ failure, and greater magnitude of lung edema.

Time-Course of Physiologic Variables During Extracorporeal Membrane Oxygenation and Outcome of Severe Acute Respiratory Distress Syndrome.

In patients undergoing extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS), it is unknown which clinical physiologic variables should be monitored to follow the evolution of lung injury and extrapulmonary organ dysfunction and to differentiate patients according to their course. We analyzed the time-course of prospectively collected clinical physiologic variables in 83 consecutive ARDS patients undergoing ECMO at a single referral center. Selected variables-including ventilator settings, respiratory system compliance, intrapulmonary shunt, arterial blood gases, central hemodynamics, and sequential organ failure assessment (SOFA) score-were compared according to outcome at time-points corresponding to 0%, 25%, 50%, 75%, and 100% of the entire ECMO duration and daily during the first 7 days. A logistic regression analysis was performed to identify changes between ECMO start and end that independently predicted hospital mortality. Tidal volume, intrapulmonary shunt, arterial lactate, and SOFA score differentiated survivors and nonsurvivors early during the first 7 days and over the entire ECMO duration. Respiratory system compliance, PaO2/FiO2 ratio, arterial pH, and mean pulmonary arterial pressure showed distinct temporal course according to outcome over the entire ECMO duration. Lack of improvement of SOFA score independently predicted hospital mortality. In ARDS patients on ECMO, temporal trends of specific physiologic parameters differentiate survivors from non-survivors and could be used to monitor the evolution of lung injury. Progressive worsening of extrapulmonary organ dysfunction is associated with worse outcome.

Spontaneous breathing during veno-venous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has started to be applied in awake spontaneously breathing patients as an alternative to invasive mechanical ventilation. As the physiologic cardiorespiratory variability is increased in this condition, the dynamic interaction between patient respiratory activity and extracorporeal system function affects the clinical management. The effect of extracorporeal CO2 removal on patient respiratory drive is variable and not always predictable, with some patients responding to CO2 removal with a decrease in respiratory rate and effort and other patients demonstrating a persistently high work of breathing independent on CO2 unload. While the pathophysiological mechanisms of this different interactions are still to be clarified, improved monitoring ability is needed both to titrate the support in responders and to avoid the risk of ventilation injury in non-responders. Acute changes in patient respiratory patterns may also occur during spontaneous breathing, making it difficult to maintain constant levels of extracorporeal respiratory support, also because changes in the distribution of venous blood volume due to lung-heart interactions affect extracorporeal blood flow. Assessment of native lung function and of its evolution over time is challenging while respiratory gas exchanges are provided by the extracorporeal system, since both oxygenation and decarboxylation capabilities can be fully evaluated only when alveolar ventilation is restored reducing extracorporeal CO2 removal. The rationale for using "awake ECMO" varies across different types of acute respiratory failure: the pathophysiological mechanisms of the underlying disease affect the patient-ECMO interaction and the goal of support. In this review we discuss the pathophysiology, technical challenges and monitoring issues of the use of ECMO in awake spontaneously breathing patients with acute respiratory failure of different etiologies.

Spontaneous Breathing during Extracorporeal Membrane Oxygenation in Acute Respiratory Failure.

BACKGROUND: We evaluate the clinical feasibility of spontaneous breathing on extracorporeal membrane oxygenation and the interactions between artificial and native lungs in patients bridged to lung transplant or with acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome. METHODS: The clinical course of a total of 48 patients was analyzed. Twenty-three of 48 patients were enrolled in the prospective study (nine bridged to lung transplant, six COPD, and eight acute respiratory distress syndrome). The response to the carbon dioxide removal was evaluated in terms of respiratory rate and esophageal pressure swings by increasing ("relief" threshold) and decreasing ("distress" threshold) the extracorporeal membrane oxygenation gas flow, starting from baseline condition. RESULTS: Considering all 48 patients, spontaneous breathing extracorporeal membrane oxygenation was performed in 100% bridge to lung transplant (9 of 9 extubated), 86% COPD (5 of 6 extubated), but 27% acute respiratory distress syndrome patients (6 of 8 extubated; P < 0.001) and was maintained for 92, 69, and 38% of the extracorporeal membrane oxygenation days (P = 0.021), respectively. In all the 23 patients enrolled in the study, gas flow increase (from 2.3 ± 2.2 to 9.2 ± 3.2 l/min) determined a decrease of both respiratory rate (from 29 ± 6 to 8 ± 9 breaths/min) and esophageal pressure swings (from 20 ± 9 to 4 ± 4 cm H2O; P < 0.001 for all). All COPD and bridge to lung transplant patients were responders (reached the relief threshold), while 50% of acute respiratory distress syndrome patients were nonresponders. CONCLUSIONS: Carbon dioxide removal through extracorporeal membrane oxygenation relieves work of breathing and permits extubation in many patients, mainly bridge to lung transplant and COPD. Only few patients with acute respiratory distress syndrome were able to perform the spontaneous breathing trial, and in about 50% of these, removal of large amount of patient's carbon dioxide production was not sufficient to prevent potentially harmful spontaneous respiratory effort.

"Awake" extracorporeal membrane oxygenation (ECMO): pathophysiology, technical considerations, and clinical pioneering.

Venovenous extracorporeal membrane oxygenation (vv-ECMO) has been classically employed as a rescue therapy for patients with respiratory failure not treatable with conventional mechanical ventilation alone. In recent years, however, the timing of ECMO initiation has been readdressed and ECMO is often started earlier in the time course of respiratory failure. Furthermore, some centers are starting to use ECMO as a first line of treatment, i.e., as an alternative to invasive mechanical ventilation in awake, non-intubated, spontaneously breathing patients with respiratory failure ("awake" ECMO). There is a strong rationale for this type of respiratory support as it avoids several side effects related to sedation, intubation, and mechanical ventilation. However, the complexity of the patient-ECMO interactions, the difficulties related to respiratory monitoring, and the management of an awake patient on extracorporeal support together pose a major challenge for the intensive care unit staff. Here, we review the use of vv-ECMO in awake, spontaneously breathing patients with respiratory failure, highlighting the pros and cons of this approach, analyzing the pathophysiology of patient-ECMO interactions, detailing some of the technical aspects, and summarizing the initial clinical experience gained over the past years.

Organ allocation waiting time during extracorporeal bridge to lung transplant affects outcomes.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTX) is still being debated. METHODS: We performed a retrospective two-center analysis of the relationship between ECMO bridging duration and survival in 25 patients. Further survival analysis was obtained by dividing the patients according to waiting time on ECMO: up to 14 days (Early group) or longer (Late group). We also analyzed the impact of the ventilation strategy during ECMO bridging (ie, spontaneous breathing and noninvasive ventilation [NIV] or intubation and invasive mechanical ventilation [IMV]). RESULTS: Seventeen of 25 patients underwent a transplant (with a 76% 1-year survival), whereas eight patients died during bridging. In the 17 patients who underwent a transplant, mortality was positively related to waiting days until LTX (hazard ratio [HR], 1.12 per day; 95% CI, 1.02-1.23; P = .02), and the Early group showed better Kaplan-Meier curves (P = .02), higher 1-year survival rates (100% vs 50%, P = .03), and lower morbidity (days on IMV and length of stay in ICU and hospital). During the bridge to transplant, mortality increased steadily with time. Considering the overall outcome of the bridging program (25 patients), bridge duration adversely affected survival (HR, 1.06 per day; 95% CI, 1.01-1.11; P = .015) and 1-year survival (Early, 82% vs Late, 29%; P = .015). Morbidity indexes were lower in patients treated with NIV during the bridge. CONCLUSIONS: The duration of the ECMO bridge is a relevant cofactor in the mortality and morbidity of critically ill patients awaiting organ allocation. The NIV strategy was associated with a less complicated clinical course after LTX.

Extracorporeal membrane oxygenation with spontaneous breathing as a bridge to lung transplantation.

OBJECTIVES: A large number of transplantation centres consider extracorporeal membrane oxygenation as an inappropriate option for bridging critical patients to lung transplantation. Technical improvements such as the introduction of a polymethylpentene membrane, new centrifugal pumps and heparin-coated circuits have led to a safer application of extracorporeal membrane oxygenation, and an increasing number of centres are reporting their positive experiences. The aim of this study was to review our practice in bridging critical candidates to lung transplantation with extracorporeal membrane oxygenation, by comparing patients with invasive mechanical ventilation with patients with spontaneous breathing. METHODS: The records of candidates for lung transplantation treated with extracorporeal membrane oxygenation have been revised. RESULTS: From February 2008 to 2012, 11 patients who experienced an abrupt worsening of their respiratory conditions were treated with extracorporeal membrane oxygenation; mean age: 33.9 ± 13.2 years, male/female ratio: 5/6, 6 patients were affected by cystic fibrosis, 2 had chronic rejection after transplantation, 2 had pulmonary fibrosis and 1 had systemic sclerosis. Seven patients were awake, while 4 patients received invasive mechanical ventilation. The sequential organ failure assessment score significantly increased during bridging time and this increase was significantly higher in the intubated patients. All the patients had bilateral lung transplantation. Spontaneously breathing patients showed a tendency to require a shorter duration of invasive mechanical ventilation, intensive care unit stay and hospital stay after transplantation. One-year survival rate was 85.7% in patients with spontaneous breathing vs 50% in patients with invasive mechanical ventilation. CONCLUSIONS: Extracorporeal membrane oxygenation in spontaneously breathing patients is a feasible, effective and safe bridge to lung transplantation.

Preemptive port site local anesthesia in gynecologic laparoscopy: a randomized, controlled trial.

STUDY OBJECTIVE: To assess the impact of preemptive infiltration of port site with local anesthetic on postlaparoscopy pain. DESIGN: Randomized, double-blind, controlled trial (Canadian Task Force classification I). SETTING: Two university hospitals. PATIENTS: A total of 170 women scheduled for gynecologic laparoscopic procedures were randomly assigned to pre-incisional infiltration with ropivacaine (n = 86) or with saline solution (n = 84). INTERVENTIONS: Infiltration with either local anesthetic or placebo was accomplished in each port site before skin incision. All patients underwent standard anesthesia induction and maintenance. MEASUREMENTS AND MAIN RESULTS: Postoperative pain was evaluated with a visual analogue scale and patient interview at 1, 3, and 24 hours after surgery. No difference was found between groups in pain levels, pain location, or in the site of superficial pain at any of the postoperative time periods. The proportion of women requiring analgesia before discharge was similar in the local anesthetic group and in the saline group (22/86 [25.6%] vs 19/84 [22.6%], p = .72). The analgesic consumption in the first 24 hours after surgery and the time to first analgesic request did not differ significantly between the two groups. CONCLUSION: Preemptive infiltration of trocar sites with ropivacaine is not effective in postoperative pain relief.

The safety of antithrombotic therapy during pregnancy.

A number of clinical conditions can require the use of antithrombotic drugs during pregnancy. These mainly include prevention of venous thromboembolism (VTE) and fetal complications in high-risk patients, treatment of VTE and prevention of arterial emboli in patients with mechanical heart valve prostheses. However, there are several problems when using antithrombotic drugs during pregnancy. Warfarin, as well as the other coumarin compounds, crosses the placenta and has the potential to cause both bleeding in the fetus and teratogenicity, therefore its use is not recommended during the first trimester and during the perinatal period. Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) do not cross the placenta and are safe for the fetus, but long-term treatment with UFH is problematic because of its inconvenient administration, the need to monitor anticoagulant activity and because of its potential side effects, such as heparin-induced thrombocytopenia and osteoporosis. LMWH is the drug of choice in the prevention and treatment of VTE during pregnancy because of its practical advantages over UFH and because of a lower risk of side effects. Patients with mechanical heart valve prostheses represent a major clinical challenge. Warfarin, the drug of choice in non-pregnant women, can be administered between the 12th and 36th week. Full-dose UFH is recommended in the first trimester and after week 36. The use of LMWH as an alternative to UFH is still a matter of debate, because inadequate data are available.

Partial liquid ventilation and positive end-expiratory pressure reduce ventilator-induced lung injury in an ovine model of acute respiratory failure.

OBJECTIVE: To examine the isolated and combined effects of positive end-expiratory pressure (PEEP) and partial liquid ventilation (PLV) on the development of ventilator-induced lung injury in an ovine model. DESIGN: Prospective controlled animal study. SETTING: University-based cardiovascular animal physiology laboratory. SUBJECTS: Thirty-eight anesthetized supine sheep weighing 22.3 +/- 2.2 kg. INTERVENTIONS: Animals were ventilated for 6 hrs (respiratory rate, 15; FIO2, 1.0, inspiratory/expiratory ratio, 1:1) with one of five pressure-controlled strategies, expressed as peak inspiratory pressure (PIP)/PEEP: low-PIP, 25/5 cm H2O (n = 8); high-PIP, 50/5 cm H2O (n = 8); high-PIP-PLV, 50/5 cm H2O-PLV (n = 8); high-PEEP, 50/20 cm H2O (n = 7); and high-PEEP-PLV, 50/20 cm H2O-PLV (n = 7). MEASUREMENTS AND MAIN RESULTS: Compared with the low-PIP control, high-PIP ventilation increased airleak, shunt, histologic evidence of lung injury, neutrophil infiltrates, and wet lung weight. Maintaining PEEP at 20 cm H2O or adding PLV reduced the development of physiologic shunt and dependent histologic injury indexes. Neither higher PEEP nor PLV reduced the high incidence of barotrauma observed in high-PIP animals. CONCLUSIONS: We conclude that application of PLV or PEEP at 20 cm H2O may improve gas exchange and afford lung protection from ventilator-induced lung injury during high-pressure mechanical ventilation in this model.