Intraoperative individualization of positive-end-expiratory pressure through electrical impedance tomography or esophageal pressure assessment: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review of randomized-controlled trials (RCTs) with meta-analyses aimed to compare the effects on intraoperative arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2), exerted by positive end-expiratory pressure (PEEP) individualized trough electrical impedance tomography (EIT) or esophageal pressure (Pes) assessment (intervention) vs. PEEP not tailored on EIT or Pes (control), in patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach. METHODS: PUBMED®, EMBASE®, and Cochrane Controlled Clinical trials register were searched for observational studies and RCTs from inception to the end of August 2022. Inclusion criteria were: RCTs comparing PEEP titrated on EIT/Pes assessment vs. PEEP not individualized on EIT/Pes and reporting intraoperative PaO2/FiO2. Two authors independently extracted data from the enrolled investigations. Data are reported as mean difference and 95% confidence interval (CI). RESULTS: Six RCTs were included for a total of 240 patients undergoing general anesthesia for surgery, of whom 117 subjects in the intervention group and 123 subjects in the control group. The intraoperative mean PaO2/FiO2 was 69.6 (95%CI 32.-106.4 ) mmHg higher in the intervention group as compared with the control group with 81.4% between-study heterogeneity (p < 0.01). However, at meta-regression, the between-study heterogeneity diminished to 44.96% when data were moderated for body mass index (estimate 3.45, 95%CI 0.78-6.11, p = 0.011). CONCLUSIONS: In patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach, PEEP personalized by EIT or Pes allowed the achievement of a better intraoperative oxygenation compared to PEEP not individualized through EIT or Pes. PROSPERO REGISTRATION NUMBER: CRD 42021218306, 30/01/2023.

Relationship between intensive care surge capacity and hospital factors: an extensive experience.

As a prolonged surge scenario, the COVID-19 pandemic has offered an unparalleled opportunity to improve hospital surge capacity (SC) understanding and the ability to manage it. In this study, the authors report the experience of a large hospital network and evaluate potential relationships between Intensive Care Units SC (ICU-SC) and some hospital-related variables: bed occupancy, emergency department admissions, ward admission from ED, and elective surgery procedures. Pearson's partial correlation coefficient (r) has been used to define the relationship between SC and the daily values of the above variables, collected through a dedicated digital platform that also ensured a regular quality check of the data. The observation has concerned several levels of analysis, namely two different types of SC calculation (SC base-SCb and SC actual-SCa), hospital category level and multi-hospital level, and two consecutive pandemic waves. Among the 16 hospitals observed, the correlation was shown to be moderate-positive with non-ICU bed occupancy (r/ = 0.62, r/ = 0.54), strong/moderate with ICU bed occupancy (r/ = 0.72, r/ = 0.54), and moderate with ward admissions from ED (r/ = 0.50, r/ = 0.51) On the contrary, the correlation proved to be moderate-negative with ED admissions (r/ = - 0.69, r/ = - 0.62) and low with the number of elective surgery procedures (r/ = - 0.10, r/ = - 0.16). This study identified a positive correlation between SC and three variables monitored: ICU bed occupancy, non-ICU bed occupancy, and ward admissions from ED. On the contrary, the correlation was negative for ED admission and the number of elective surgery procedures. The results have been confirmed across all levels of analysis adopted.

In-Hospital Predictors of Need for Ventilatory Support and Mortality in Chest Trauma: A Multicenter Retrospective Study.

Chest trauma management often requires the use of invasive and non-invasive ventilation. To date, only a few studies investigated the predictors of the need for ventilatory support. Data on 1080 patients with chest trauma managed in two different centers were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the predictors of tracheal intubation (TI), non-invasive mechanical ventilation (NIMV), and mortality. Rib fractures (p = 0.0001) fracture of the scapula, clavicle, or sternum (p = 0.045), hemothorax (p = 0.0035) pulmonary contusion (p = 0.0241), and a high Injury Severity Score (ISS) (p ≤ 0001) emerged as independent predictors of the need of TI. Rib fractures (p = 0.0009) hemothorax (p = 0.0027), pulmonary contusion (p = 0.0160) and a high ISS (p = 0.0001) were independent predictors of NIMV. The center of trauma care (p = 0.0279), age (p < 0.0001) peripheral oxygen saturation in the emergency department (p = 0.0010), ISS (p < 0.0001), and Revised Trauma Score (RTS) (p < 0.0001) were independent predictors of outcome. In conclusion, patients who do not require TI, while mandating ventilatory support with selected types of injuries and severity scores, are more likely to be subjected to NIMV. Trauma team expertise and the level of the trauma center could influence patient outcomes.

Association between ambulance prehospital time and maternal and perinatal outcomes in Sierra Leone: a countrywide study.

INTRODUCTION: Sierra Leone, one of the countries with the highest maternal and perinatal mortality in the world, launched its first National Emergency Medical Service (NEMS) in 2018. We carried out a countrywide assessment to analyse NEMS operational times for obstetric emergencies in respect the access to timely essential surgery within 2 hours. Moreover, we evaluated the relationship between operational times and maternal and perinatal mortality. METHODS: We collected prehospital data of 6387 obstetric emergencies referrals from primary health units to hospital facilities between June 2019 and May 2020 and we estimated the proportion of referrals with a prehospital time (PT) within 2 hours. The association between PT and mortality was investigated using Poisson regression models for binary data. RESULTS: At the national level, the proportion of emergency obstetric referrals with a PT within 2 hours was 58.5% (95% CI 56.9% to 60.1%) during the rainy season and 61.4% (95% CI 59.5% to 63.2%) during the dry season. Results were substantially different between districts, with the capital city of Freetown reporting more than 90% of referrals within the benchmark and some rural districts less than 40%. Risk of maternal death at 60, 120 and 180 min of PT was 1.8%, 3.8% and 4.3%, respectively. Corresponding figures for perinatal mortality were 16%, 18% and 25%. CONCLUSION: NEMS operational times for obstetric emergencies in Sierra Leone vary greatly and referral transports in rural areas struggle to reach essential surgery within 2 hours. Maternal and perinatal risk of death increased concurrently with operational times, even beyond the 2-hour target, therefore, any reduction of the time to reach the hospital, may translate into improved patient outcomes.

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients.

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Cerebral nervous system vasculitis in a Covid-19 patient with pneumonia.

We describe a patient affected by Covid-19 acute respiratory distress syndrome with a cerebral nervous system vasculitis triggered by SARS-Cov-2, managed at the University hospital, in Novara, Italy in the area most impacted by the pandemic and where 749 Covid-19 positive patients were admitted from March 1st until April 25th, 2020.

Inferior Vena Cava Filter in a Patient with COVID-19 Pneumonia to Prevent a Massive Pulmonary Embolism.

COVID 19 predispose to deep vein thrombosis. We describe an early placement of inferior vena cava filter added to the therapeutic anticoagulation to prevent a massive pulmonary embolism.

Mechanical Ventilation Guided by Uncalibrated Esophageal Pressure May Be Potentially Harmful.

BACKGROUND: Esophageal balloon calibration was proposed in acute respiratory failure patients to improve esophageal pressure assessment. In a clinical setting characterized by a high variability of abdominal load and intrathoracic pressure (i.e., pelvic robotic surgery), the authors hypothesized that esophageal balloon calibration could improve esophageal pressure measurements. Accordingly, the authors assessed the impact of esophageal balloon calibration compared to conventional uncalibrated approach during pelvic robotic surgery. METHODS: In 30 adult patients, scheduled for elective pelvic robotic surgery, calibrated end-expiratory and end-inspiratory esophageal pressure, and the associated respiratory variations were obtained at baseline, after pneumoperitoneum-Trendelenburg application, and with positive end-expiratory pressure (PEEP) administration and compared to uncalibrated values measured at 4-ml filling volume, as per manufacturer recommendation. Data are expressed as median and [25th, 75th percentile]. RESULTS: Ninety calibrations were successfully performed. Chest wall elastance worsened with pneumoperitoneum-Trendelenburg and PEEP (19.0 [15.5, 24.6] and 16.7 [11.4, 21.7] cm H2O/l) compared to baseline (8.8 [6.3, 9.8] cm H2O/l; P < 0.0001 for both comparisons). End-expiratory and end-inspiratory calibrated esophageal pressure progressively increased from baseline (3.7 [2.2, 6.0] and 7.7 [5.9, 10.2] cm H2O) to pneumoperitoneum-Trendelenburg (6.2 [3.8, 10.2] and 16.1 [13.1, 20.6] cm H2O; P = 0.014 and P < 0.001) and PEEP (8.8 [7.7, 15.6] and 18.9 [16.3, 22.0] cm H2O; P < 0.0001 vs. baseline for both comparison; P < 0.001 and P = 0.002 vs. pneumoperitoneum-Trendelenburg) and, at each study step, they were persistently lower than uncalibrated esophageal pressure (P < 0.0001 for all comparisons). Overall, difference among uncalibrated and calibrated esophageal pressure was 5.1 [3.8, 8.4] cm H2O at end-expiration and 3.8 [3.0, 6.3] cm H2O at end-inspiration. Uncalibrated esophageal pressure swing was always lower than calibrated one (P < 0.0001 for all comparisons) with a difference of -1.0 [-1.8, -0.4] cm H2O. CONCLUSIONS: In a clinical setting with variable chest wall mechanics, uncalibrated measurements substantially overestimated absolute values and underestimated respiratory variations of esophageal pressure. Calibration could substantially improve mechanical ventilation guided by esophageal pressure.

Esophageal Pressure Versus Gas Exchange to Set PEEP During Intraoperative Ventilation.

BACKGROUND: Pneumoperitoneum and Trendelenburg position affect respiratory system mechanics and oxygenation during elective pelvic robotic surgery. The primary aim of this randomized pilot study was to compare the effects of a conventional low tidal volume ventilation with PEEP guided by gas exchange (VGas-guided) versus low tidal volume ventilation tailoring PEEP according to esophageal pressure (VPes-guided) on oxygenation and respiratory mechanics during elective pelvic robotic surgery. METHODS: This study was conducted in a single-center tertiary hospital between September 2017 and January 2019. Forty-nine adult patients scheduled for elective pelvic robotic surgery were screened; 28 subjects completed the full analysis. Exclusion criteria were American Society of Anesthesiologists physical status ≥ 3, contraindications to nasogastric catheter placement, and pregnancy. After dedicated naso/orogastric catheter insertion, subjects were randomly assigned to VGas-guided ([Formula: see text] and PEEP set to achieve [Formula: see text] > 94%) or VPes-guided (PEEP tailored to equalize end-expiratory transpulmonary pressure). Oxygenation ([Formula: see text]/[Formula: see text]) was evaluated (1) at randomization, after pneumoperitoneum and Trendelenburg application; (2) at 60 min; (3) at 120 min following randomization; and (4) at end of surgery. Respiratory mechanics were assessed during the duration of the study. RESULTS: Compared to VGas-guided, oxygenation was higher with VPes-guided at 60 min (388 ± 90 vs 308 ± 95 mm Hg, P = .02), at 120 min after randomization (400 ± 90 vs 308 ± 81 mm Hg, P = .008), and at the end of surgery (402 ± 95 vs 312 ± 95 mm Hg, P = .009). Respiratory system elastance was lower with VPes-guided compared to VGas-guided at 20 min (24.2 ± 7.3 vs 33.4 ± 10.7 cm H2O/L, P = .001) and 60 min (24.1 ± 5.4 vs 31.9 ± 8.5 cm H2O/L, P = .006) from randomization. CONCLUSIONS: Oxygenation and respiratory system mechanics were improved when applying a ventilatory strategy tailoring PEEP to equalize expiratory transpulmonary pressure in subjects undergoing pelvic robotic surgery compared to a VGas-guided approach. (ClinicalTrials.gov registration NCT03153592).

Oesophageal balloon calibration during pressure support ventilation: a proof of concept study.

Oesophageal balloon calibration improves the oesophageal pressure (Pes) assessment during invasive controlled mechanical ventilation. The primary aim of the present investigation was to ascertain the feasibility of oesophageal balloon calibration during pressure support ventilation (PSV). Secondarily, the calibrated Pes (Pescal) was compared to uncalibrated one acquired at 4 ml-filling volume (PesV4), as per manufacturer recommendation. After a naso-gastric tube equipped with oesophageal balloon was correctly positioned in 21 adult patients undergoing invasive volume-controlled ventilation (VCV) for acute hypoxemic respiratory failure, the balloon was progressively inflated, applying a series of end-inspiratory and end-expiratory holds at each filling volume during VCV and PSV. Upon optimal balloon filling volume (Vbest) was identified, Pescal was computed by correcting the Pes measured at Vbest for the oesophageal wall pressure elicited at same filling volume. Finally, end-expiratory and end-inspiratory PesV4 were recorded too. A total of 42 calibrations, 21 per ventilatory mode, were performed. Vbest was 1.9 ± 1.6 ml in VCV and 1.7 ± 1.6 ml in PSV (p = 0.5217). PesV4 was overestimated compared to Pescal at end-expiration and end-inspiration (p <0.0001 for all comparisons) in both VCV (13.4 ± 3.4 cmH2O and 15.4 ± 3 cmH2O vs. 8.5 ± 2.9 cmH2O and 11.4 ± 3 cmH2O) and PSV (14.7 ± 4.2 cmH2O and 17 ± 3.9 cmH2O vs. 8.9 ± 3.4 cmH2O and 12.4 ± 3.9 cmH2O). In PSV, oesophageal balloon calibration is feasible and allows to obtain a reliable Pes assessment compared to uncalibrated approach.

Assessment of Fluid Responsiveness in Prone Neurosurgical Patients Undergoing Protective Ventilation: Role of Dynamic Indices, Tidal Volume Challenge, and End-Expiratory Occlusion Test.

BACKGROUND: In patients in the prone position, the reliability of pulse pressure variation and stroke volume variation (PPV and SVV) and the use of functional hemodynamic tests to predict fluid responsiveness have not previously been established. Perioperatively, in this setting, optimizing fluid management can be challenging, and fluid overload is associated with both intraoperative and postoperative complications. We designed this study to assess the sensitivity and specificity of baseline PPV and SVV, the tidal volume (VT) challenge (VTC) and the end-expiratory occlusion test (EEOT) in predicting fluid responsiveness during elective spinal surgery. METHODS: The study protocol was started during a period of intraoperative hemodynamic stability after prone positioning and before the administration of any vasopressor: (1) at baseline, the controlled ventilation was set at 6 mL/kg of predicted body weight (PBW) (T0); (2) patients underwent the first EEOT (EEOT6) by interrupting the mechanical ventilation for 30 seconds; (3) the ventilation was set again at 6 mL/kg PBW for 1 minute (T1); (4) the VTC was applied by increasing the VT up to 8 mL/kg PBW for 1 minute; (5) the ventilation was kept at 8 mL/kg PBW for 1 minute (T2); (6) a second EEOT (EEOT8) was performed; (7) the VT was reduced back to 6 mL/kg PBW for 1 minute (T3); (8) a fluid challenge of 250 mL of Ringer's solution was infused over 10 minutes. After each step, a complete set of hemodynamic measurements was recorded. RESULTS: Neither PPV and SVV values recorded at T3 nor the EEOT6 or the EEOT8 predicted fluid responsiveness. The change in PPV after VTC application predicted fluid responsiveness with an area under the curve of 0.96 (95% confidence interval, 0.87-1.00), showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 12.2%. The change in SVV after VTC application predicted fluid responsiveness with an area under the curve 0.96 (95% confidence interval, 0.89-1.00) showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 8.0%. A linear correlation between stroke volume index changes after fluid challenge administration and the changes in PPV and SVV after VTC application was observed (r = 0.71; P < .0001 and r = 0.68; P < .0001, respectively). CONCLUSIONS: In prone elective neurosurgical patients, the baseline values of PPV and SVV and the EEOT fail to predict fluid responsiveness, while the VTC is a very reliable functional hemodynamic test and could be helpful in guiding intraoperative fluid therapy.

Intra-operative low-dose ketamine does not reduce the cost of post-operative pain management after surgery: a randomized controlled trial in a low-income country.

BACKGROUND: In developing countries, post-operative pain remains underestimated and undertreated due to economic constraints, lack of awareness and limited resources. In contrast, ketamine is an effective, readily available, easy to use and inexpensive drug frequently used in poor settings. OBJECTIVES: The aim of this study was to explore the overall reduction in the medication treatment cost of acute post-operative pain by adding intra-operative low-dose ketamine to traditional intravenous morphine for surgery in a low-income country. METHODS: A double blind randomized controlled trial with placebo-controlled parallel group was performed in Mulago National Hospital (Uganda). Consenting adults scheduled for elective surgery were randomized into two study arms: Group K received ketamine 0.15mg/kg bolus at induction and a continuous infusion of 0.12 mg/kg/hour till start of skin closure; Group C (control) received normal saline. Both groups received Morphine 0.1 mg/kg IV at debulking. The total medication cost was registered. NRS pain scores and other measurements such vital signs and incidence of major and minor side effects were also recorded. RESULTS: A total of 46 patients were included. Patients' baseline characteristics were comparable in both groups. No statistically significant difference was found between the groups concerning the overall medication cost of post-operative pain management. Pain scores, patients' satisfaction in the first 24 hours after surgery and hospital length of stay were similar in both groups. CONCLUSION: Our results do not support the utilization of intra-operative low dose ketamine as a cost-saving post-operative pain treatment strategy for all types of surgery in low-resource settings.

Perfluorocarbon solutions limit tubular epithelial cell injury and promote CD133+ kidney progenitor differentiation: potential use in renal assist devices for sepsis-associated acute kidney injury and multiple organ failure.

Background: The renal assist device (RAD) is a blood purification system containing viable renal tubular epithelial cells (TECs) that has been proposed for the treatment of acute kidney injury (AKI) and multiple organ failure. Perfluorocarbons (PFCs) are oxygen carriers used for organ preservation in transplantation. The aim of this study was to investigate the effect of PFCs on hypoxia- and sepsis-induced TEC injury and on renal CD133+ progenitor differentiation in a microenvironment similar to the RAD. Methods: TECs were seeded in a polysulphone hollow fibre under hypoxia or cultured with plasma from 10 patients with sepsis-associated AKI in the presence or absence of PFCs and were tested for cytotoxicity (XTT assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay, caspases, enzyme-linked immunosorbent assay, Fas/Fas Ligand pathway activation), mitochondrial activity, cell polarity [transepithelial electrical resistance (TEER)] and adenosine triphosphate production. The effect of PFCs on proliferation and differentiation of human CD133+ progenitors was also studied. Results: In the presence of PFCs, TECs seeded into the polysulphone hollow fibre showed increased viability and expression of insulin-like growth factor 1, hepatocyte growth factor and macrophage-stimulating protein. Plasma from septic patients induced TEC apoptosis, disruption of oxidative metabolism, alteration of cell polarity and albumin uptake, down-regulation of the tight junction protein ZO-1 and the endocytic receptor megalin on the TEC surface. These detrimental effects were significantly reduced by PFCs. Moreover, PFCs induced CD133+ renal progenitor cell proliferation and differentiation towards an epithelial/tubular-like phenotype. Conclusions: PFCs improved the viability and metabolic function of TECs seeded within a polysulphone hollow fibre and subjected to plasma from septic AKI patients. Additionally, PFCs promoted differentiation towards a tubular/epithelial phenotype of CD133+ renal progenitor cells.

Renal hypoperfusion and impaired endothelium-dependent vasodilation in an animal model of VILI: the role of the peroxynitrite-PARP pathway.

INTRODUCTION: Mechanical ventilation (MV) can injure the lungs and contribute to an overwhelming inflammatory response, leading to acute renal failure (ARF). We previously showed that poly(adenosine diphosphate-ribose) polymerase (PARP) is involved in the development of ventilator-induced lung injury (VILI) and the related ARF, but the mechanisms underneath remain unclear. In the current study we therefore tested the hypothesis that renal blood flow and endothelial, functional and tissue changes in the kidney of rats with lipopolysaccharide (LPS)-induced lung injury aggravated by MV, is caused, in part, by activation of PARP by peroxynitrite. METHODS: Anesthetized Sprague Dawley rats (n = 31), were subjected to intratracheal instillation of lipopolysaccharide at 10 mg/kg followed by 210 min of mechanical ventilation at either low tidal volume (6 mL/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (19 mL/kg) with zero positive end-expiratory pressure in the presence or absence of a peroxynitrite decomposition catalyst, WW85 or a PARP inhibitor, PJ-34. During the experiment, hemodynamics and blood gas variables were monitored. At time (t) t = 0 and t = 180 min, renal blood flow was measured. Blood and urine were collected for creatinine clearance measurement. Arcuate renal arteries were isolated for vasoreactivity experiment and kidneys snap frozen for staining. RESULTS: High tidal volume ventilation resulted in lung injury, hypotension, renal hypoperfusion and impaired renal endothelium-dependent vasodilation, associated with renal dysfunction and tissue changes (leukocyte accumulation and increased expression of neutrophil gelatinase-associated lipocalin). Both WW85 and PJ-34 treatments attenuated lung injury, preserved blood pressure, attenuated renal endothelial dysfunction and maintained renal blood flow. In multivariable analysis, renal blood flow improvement was, independently from each other, associated with both maintained blood pressure and endothelium-dependent vasodilation by drug treatment. Finally, drug treatment improved renal function and reduced tissue changes. CONCLUSIONS: The peroxynitrite-induced PARP activation is involved in renal hypoperfusion, impaired endothelium-dependent vasodilation and resultant dysfunction, and injury, in a model of lung injury.

Serum levels of osteopontin are increased in SIRS and sepsis.

OBJECTIVE: In sepsis, dysregulation of the immune response leads to rapid multiorgan failure and death. Accurate and timely diagnosis is lifesaving and should discriminate sepsis from the systemic inflammatory response syndrome (SIRS) caused by non-infectious agents. Osteopontin acts as an extracellular matrix component or a soluble cytokine in inflamed tissues. Its exact role in immune response and sepsis remains to be elucidated. Therefore, we investigated the role of osteopontin in SIRS and sepsis. DESIGN: Prospective, observational study. SETTING: Intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Fifty-six patients with SIRS or sepsis and 56 healthy subjects were enrolled. INTERVENTIONS: We analyzed the serum levels of osteopontin and TH1-TH2 cytokines and investigated the role of osteopontin on interleukin 6 secretion by monocytes. MEASUREMENTS AND MAIN RESULTS: Serum osteopontin levels were strikingly higher in patients than in controls and in sepsis than in SIRS, and decreased during the resolution of both the disorders. Receiver operating characteristic curves showed that osteopontin levels have discriminative power between SIRS and sepsis with an area under the curve of 0.796. Osteopontin levels directly correlated with those of interleukin 6 and in vitro, recombinant osteopontin increased interleukin 6 secretion by monocytes in both the absence and presence of high doses of lipopolysaccharide. CONCLUSION: These data suggest that osteopontin might be a mediator involved in the pathogenesis of SIRS and sepsis, possibly by supporting interleukin 6 secretion. DESCRIPTOR: 45. SIRS/Sepsis: clinical studies.

Inhibition of poly(adenosine diphosphate-ribose) polymerase attenuates ventilator-induced lung injury.

BACKGROUND: Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury. METHODS: Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34. RESULTS: The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor alpha and interleukin 6, and attenuated the degree of apoptosis in the kidney. CONCLUSION: The pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase reduces ventilator-induced lung injury and protects kidney function.

Changes in respiratory and hemodynamic parameters during low-dose propofol sedation in combination with regional anesthesia for herniorrhaphy and genitourinary surgery in children.

BACKGROUND: Spontaneous vs mechanical ventilation during propofol sedation has been a subject of debate. We evaluated the safety of low-dose propofol sedation as an adjunct to regional anesthesia during herniorrhaphy and genitourinary surgery in infants and children. METHODS: The study was conducted in a prospective, nonrandomized manner using a consecutive sample of 62 American Society of Anesthesiologists physical status class I patients between 5 months to 11 years of age in the surgery unit of an urban University Hospital. Propofol sedation (4-8 mg x kg(-1) x h(-1) continuous infusion) was used with regional anesthesia (caudal, ilioinguinal/iliohypogastric nerve or penile block with 0.2-0.375% ropivacaine). All children were spontaneously breathing without an anesthesia circuit. Respiratory and hemodynamic parameters were continuously recorded on all patients. One-way analysis of variance (ANOVA) for repeated measurements was used to analyze changes in respiratory and hemodynamic parameters during the procedure. RESULTS: Spontaneous ventilation was maintained in all patients with minimal changes in hemodynamic parameters. Heart rate, mean arterial pressure, and P(E)CO(2) remained stable throughout the study period: 23/62 (37%) patients exhibited signs of developing intrinsic endexpiratory pressure (PEEPi) or the presence of PEEPi because of progressive reduction of expiratory time. CONCLUSIONS: Low-dose propofol sedation in combination with regional anesthesia for elective herniorrhaphy and genitourinary surgery in children maintains spontaneous ventilation and has minimal effects on hemodynamic parameters for sedation lasting <1 h. The presence of PEEPi is a relative contraindication to the use of this regimen in children with asthma or history of upper airway infections.

Fast-track approach in abdominal aortic surgery: left subcostal incision with blended anesthesia.

OBJECTIVES: The introduction of fast-tracking multidisciplinary programs allows good results in postoperative outcome in many surgical specialties. We evaluated a multimodal clinical program (based on mininvasive surgery, epidural anesthesia and early mobilization and feeding) in abdominal aortic surgery. METHODS: Between June 2000 and October 2005, 323 unselected patients were treated for atherosclerotic aorto-iliac occlusive disease (aorto-femoral bypass) and aortic or aorto-iliac aneurysm (aorto-aortic graft or aorto-iliac bifurcated graft). The infusion of bupivacaine 0.5% through an epidural catheter at T6-T7 interspace allowed sensory block between T4-S3. A light general anesthesia was performed using sevoflurane by a laryngeal mask in spontaneous breathing; no nasogastric tube was used. The patients were placed in dorsal decubitus; a transperitoneal access was performed with a left subcostal incision parallel to the condro-costal edge and spread from the linea alba to the edge of the rectus muscle. The bowel was maintained inside the abdominal cavity and manipulated with care. Standard surgical instrumentation was used. No drains were placed. Patients were transferred to the surgical ward at the end of surgery; they were early mobilized and enforced to drink and to eat. Analgesia was achieved with a continuous epidural infusion of bupivacaine 0.25% supplemented by oral ibuprofen on request. RESULTS: We observed a mortality rate of 2.5% and a low postoperative morbidity: 1.4% of cardiac complications, 3.7% of transient creatinine increase, and no pulmonary complications. All patients ambulated a mean of 536 m (95% CI: 81.4) on the day of surgery and 2544 m (95% CI: 208.9) the day after. They consumed an oral diet, 36.2% of their daily caloric requirement on the same day of surgery and 1583 Kcal (95% CI: 105.2) the day after (77% of daily caloric requirement). Median hospital stay was three days (range 2-21). All patients were discharged home. CONCLUSIONS: Our experience suggested that hospital stay and morbidity after abdominal aortic surgery can be decreased by performing a mininvasive surgical approach, thoracic epidural anesthesia-analgesia and an aggressive postoperative nursing on the ward. Therefore, this multidisciplinary program can be proposed to all patients undergoing aortic surgery without prior selection, major technological investments and long-term surveillance.