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Contains fulltext : 244115.pdf (Publisher’s version ) (Closed access) The novel coronavirus pandemic has radically changed the landscape of normal surgical practice. Lifesaving cancer surgery, however, remains a clinical priority, and there is an increasing need to fully define the optimal oncologic management of patients with varying stages of lung cancer, allowing prioritization of which thoracic procedures should be performed in the current era. Healthcare providers and managers should not ignore the risk of a bimodal peak of mortality in patients with lung cancer; an imminent spike due to mortality from acute coronavirus disease 2019 (COVID-19) infection, and a secondary peak reflecting an excess of cancer-related mortality among patients whose treatments were deemed less urgent, delayed, or cancelled. The European Association of Cardiothoracic Anaesthesiology and Intensive Care Thoracic Anesthesia Subspecialty group has considered these challenges and developed an updated set of expert recommendations concerning the infectious period, timing of surgery, vaccination, preoperative screening and evaluation, airway management, and ventilation of thoracic surgical patients during the COVID-19 pandemic.

A recent important development in thoracic surgery has been the introduction and widespread employment of video-assisted thoracoscopic surgery (VATS), which minimizes tissue injury, reduces postoperative pain and improves postoperative recovery. Since intraoperative pain is likewise reduced during VATS, less invasive anesthetic approaches during VATS such as avoiding intubation, providing monitored sedation, and maintaining spontaneous breathing during the procedure have been more recently explored and the concept of non-intubated VATS (NI-VATS) has emerged. During NI-VATS, sedatives and regional anesthesia have been used to provide sedation and pain relief during the procedures. Various modes of sedation used during NI-VATS have been shown to keep the patient comfortable while maintaining sufficient spontaneous breathing. Regional anesthesia used has ranged from epidural anesthesia to local anesthesia to intercostal nerves. In some series, local anesthetics have been applied to the vagal nerve to suppress cough during the procedure. Although no large prospective randomized trial has studied the short- and long-term efficacy and safety of NI-VATS, a large number of retrospective studies and some prospective studies show that NI-VATS is a feasible and, when indicated judiciously, a safe method of intraoperative care. Especially for minor VATS, increased turnover times in operating room, improved immediate recovery after surgery and reduction in material costs have been shown for NI-VATS. However, some concerns regarding short- and long-term safety still remain. Short term problems of emergency intubation during the procedure should be expected and considered a major difficult airway challenge. This major safety issue needs team education, possibly simulation, and proper preparation for each and every patient. The range of performable NI-VATS procedures should be determined by level of surgical and anesthetic expertise. Long term safety issues are also important in selecting patients for NI-VATS since properly randomized studies showing reduction of major morbidity and mortality in complex and long operations are lacking. This is especially the case for cancer surgery.

Objectives: There is no consensus about the optimal length of hospital stay in patients undergoing elective transfemoral TAVR under general anesthesia. Our study tried to find predictors of failure of early discharge strategy in those patients. Methods and results: We included retrospectively 135 high risk TAVI patients (mean Log. EuroSCORE 30.8 ± 6) operated under general anaesthesia between June 2017 and January 2018 in central hospital, Bad Berka, Germany. Focus on the preoperative factors was established in favor to find possible predictors of longer hospital stay in this group of patients. Uni- and multivariate analysis were performed to identify independent preoperative predictors of fast-track protocol failure, defined as inability to discharge the patient from the hospital five days after surgery. Independent predictors of fast-track protocol failure were NYHA IV (OR 4.3; CI 95% 2.3-25, p-Value 0.017), ejection fraction (EF) ≤ 30% (OR 3.5; CI 95% 2-12.5, p-Value 0.006), right bundle branch block (OR 4.7; CI 95% 1.25-25, p-Value 0.03) and stroke with residual disability (OR 4.5; CI 95% 1.1-16, p-Value 0.025). Conclusion: NYHA IV, severely reduced ejection fraction, right bundle branch block and stroke with residual disability might be considered potential predictors of failure of fast track protocol in patient undergoing TAVI under general anesthesia.

When switching from two-lung to one-lung ventilation (OLV), shunt fraction increases, oxygenation is impaired, and hypoxemia may occur. Hypoxemia during OLV may be predicted from measurements of lung function, distribution of perfusion between the lungs, whether the right or the left lung is ventilated, and whether the operation will be performed in the supine or in the lateral decubitus position. Hypoxemia during OLV may be prevented by applying a ventilation strategy that avoids alveolar collapse while minimally impairing perfusion of the dependent lung. Choice of anesthesia does not influence oxygenation during clinical OLV. Hypoxemia during OLV may be treated symptomatically by increasing inspired fraction of oxygen, by ventilating, or by using continuous positive airway pressure in the nonventilated lung. Hypoxemia during OLV may be treated causally by correcting the position of the double-lumen tube, clearing the main bronchi of the ventilated lung from secretions, and improving the ventilation strategy.

Objectives Increasing pulmonary blood flow aggravated ventilation-associated lung injury in ex vivo animal experiments, but data were less consistent in an in vivo animal model and do not reflect redistributed lung perfusion seen in clinical acute lung injury. We sought to determine the effects of increased cardiac output on markers of lung injury in an in vivo model of inhomogeneous lung perfusion and injury. Design Prospective, controlled animal study. Setting Experimental research laboratory of a university hospital. Subjects A total of 50 anesthetized, mechanically ventilated, male Wistar rats. Interventions Unilateral lung injury was induced in rats by left lung acid instillation. After 24 hrs, animals were anesthetized and subjected to mechanical ventilation (tidal volume, 8 mL/kg; positive end-expiratory pressure, 7 cm H2O; FIO2, 0.4) and continuous infusion of either 10 microg x kg x min dobutamine or isotonic saline (control) for 4 hrs. Measurements and main results Cardiac output and differential lung perfusion were recorded throughout the ventilation period. Right and left lung wet-to-dry weight ratio, cytokines and inflammatory cells in lung lavage, and histologic lung injury were measured postmortem. After acid injury, lung perfusion was preferentially distributed to the noninjured lung. Dobutamine increased baseline cardiac output (>70%) and perfusion of both lungs (left, acid-instilled lung: from 16 +/- 2 to 29 +/- 6 mL/min; right, non-acid-instilled lung: from 54 +/- 3 to 98 +/- 7 mL/min). There was no difference in left lung injury between dobutamine- and saline-infused animals, but right lung injury was aggravated in dobutamine-infused animals, as indicated by increased lung edema, histologic lung injury, and cell counts in lavage. Conclusions In the setting of unilateral lung injury and uneven lung perfusion, a dobutamine-induced increase in cardiac output has potentially detrimental effects on the opposite lung.

Background Endotoxin, when delivered shortly before or during mechanical ventilation, increases susceptibility to ventilation-associated lung injury. However, it is unclear whether increased susceptibility to ventilator-associated lung injury is still present after clinical recovery from a transient endotoxin challenge. Methods Anesthetized rats were submitted to a 4-h period of mechanical ventilation with low (8 ml/kg) or high (24, 27, or 30 ml/kg) tidal volumes (VTs) 24 h after transient illness had been provoked by a single nonlethal intravenous injection of Escherichia coli endotoxin. Control animals were injected with phosphate-buffered saline and underwent the same protocol. Results At 24 h, endotoxin-treated nonventilated animals showed no symptoms of clinical illness, and oxygenation was comparable with that of controls, but lung neutrophil counts were increased. Compared with controls, mechanical ventilation with high VT induced a stronger pulmonary inflammatory response and more severe lung injury in endotoxin-treated animals, as indicated by impaired oxygenation, increased lung wet-to-dry weight ratio, and increased levels of protein, neutrophils, and cytokines in lung lavage fluid. In addition, the highest VT resulted in increased mortality in endotoxin-treated animals. Low VT after endotoxin treatment did not cause functional pulmonary impairment but induced an inflammatory response. Conclusions In this animal model, a 24-h delay after a single systemic injection of endotoxin resulted in clinical recovery and preserved pulmonary function but did not prevent increased susceptibility to ventilator-associated lung injury provoked by high VT. Residual pulmonary inflammation and neutrophilic infiltration at initiation of mechanical ventilation probably contribute to these findings.

Background Based on the association between the neutrophil and ventilator-induced lung injury, the authors hypothesized that neutrophil inhibition with fucoidin would be beneficial and stimulation with granulocyte colony-stimulating factor (G-CSF) would be harmful in a rat model of lethal ventilator-induced lung injury. Methods Animals (n = 111) were randomly assigned to be pretreated with fucoidin, G-CSF, or placebo (control) before 4 h of low-tidal-volume (10 ml/kg) or high-tidal-volume (40 ml/kg) mechanical ventilation. Results All low-volume animals survived. With high volumes, compared with controls, fucoidin did not improve survival (3 of 20 control animals and 5 of 20 fucoidin animals died; P = 0.51) but G-CSF significantly worsened it (18 of 22 animals died; P < 0.001). Circulating neutrophils were increased early with G-CSF and late with fucoidin with low and high tidal volumes (P < 0.05 for each treatment and tidal volume). Fucoidin decreased lung neutrophils, but these were only significant with high tidal volumes, whereas G-CSF increased lung neutrophils but only significantly with low tidal volumes (P < or = 0.01 for each). Fucoidin did not alter any cardiopulmonary measure significantly. Compared with control, G-CSF increased airway pressures with high tidal volumes and worsened lung edema and arterial oxygen with both tidal volumes (P < 0.05 for each). Conclusions In this model, neutrophil stimulation by G-CSF increased lung dysfunction and with high tidal volumes worsened survival rates. Extrapolated clinically, neutrophil stimulation either by agents such as G-CSF or conditions such as sepsis may aggravate ventilator-induced lung injury.

Background: Differing factors may alter the effects of antibody to tumor necrosis factor (TNF) in infection and sepsis. The authors tested whether bacteria type or treatment route alters antibody to TNF in a rat model of bacterial pneumonia. Methods: Rats (n 231) received similarly lethal doses of either intratracheal Escherichia coli or Staphylococcus aureus followed by treatment with either intratracheal or intraperitoneal antibody to TNF or control serum. Animals received antibiotics (cefotiam daily dose, 100 mg/kg) starting 4 h after inoculation and were studied for up to 96 h. Results: Compared with S. aureus, E. coli increased serum TNF and interleukin-6 concentrations, lung lavage TNF concentrations, neutrophil counts, and alveolar-to-arterial oxygen gradients and decreased circulating neutrophils and lymphocytes (P > 0.05 for all). Compared with controls, with both bacteria, except for lung lavage TNF concentrations (which decreased with intratracheal but not with intraperitoneal antibody to TNF), treatment route did not alter the effects of antibody to TNF on any parameter (P not significant for all). Antibody to TNF reduced mortality rates (relative risk of death SEM) with both E. coli (1.6 0.6; P 0.006) and S. aureus (0.5 0.04; P 0.185), but these reductions were greater with E. coli than with S. aureus in a trend approaching statistical significance (P 0.09). Compared with controls, similarly (P not significant) with both bacteria, antibody to TNF decreased lung lavage and tissue bacteria concentrations (both P < 0.05) and serum TNF concentration (P < 0.09) and increased circulating neutrophils and lymphocytes (both P < 0.01). Compared with S. aureus, with E. coli antibody to TNF decreased alveolar-to-arterial oxygen gradients (P 0.04) and increased serum interleukin-6 concentrations (P 0.003). Conclusion: Antibody to TNF improved host defense and survival rates with both lethal E. coli and S. aureus pneumonia, but protection was greater with E. coli, where TNF concentrations were higher than with S. aureus. The efficacy of antiinflammatory agents in sepsis may be altered by bacteria type. AN excessive host inflammatory response has been closely associated with the organ injury and lethality related to sepsis and septic shock. 1 Of the mediators activated and released during this response, tumor necrosis factor (TNF) was one of the first to be directly associated with these pathogenetic events during sepsis. 2 On the basis of this, over the past decade several different agents were developed to specifically inhibit TNF in patients with sepsis. Although these therapies were very beneficial in published animal models of sepsis, 2–25 none showed individual benefit in 10 clinical trials enrolling more than 5,000 patients. 26 –37 A review of this experience however shows that although these agents were tested almost exclusively in animal models using Gram-negative infectious challenges, patients in clinical trials presented with sepsis related to differing types of underlying infection, including Gram-negative, Gram-positive, and mixed bacterial infections. 2–37 Thus, variability in the release or activity of TNF with differing types of bacteria might provide one basis for the disparate effects antibody to TNF agents had in comparing preclinical and clinical trials. 38 Although TNF may be a central host mediator in tissue injury during Gram-negative bacterial infection, other mediators may play a more important role with other bacteria types. In several different studies, the TNF response with Grampositive bacterial challenge has been shown to be either diminished or retarded when compared with Gram-negative bacterial challenges. 39 –4 1 Consistent with this possibility, we showed before that similarly lethal doses of Escherichia coli and Staphylococcus aureus administered intratracheally in rats resulted in significantly greater TNF concentrations with the former than with the latter bacteria type. 42 Furthermore, administration of granulocyte colony-stimulating factor to augment host defense function with these challenges, although increasing circulating neutrophils and survival rates with S. aureus, caused a paradoxical reduction in circulating neutrophils and worsened lung injury and survival rates with E. coli. Thus, in this preclinical model, stimulating the neutrophil, a cellular component in the inflammatory response, had very different effects comparing similarly lethal E. coli and S. aureus pneumonia. This differential effect of granulocyte colony-stimulating factor with Gram-positive bacterial pneumonia has now been observed in clinical trials testing this agent. 43

We investigated whether decreases in circulating polymorphonuclear neutrophils (PMN) during lethal Escherichia coli ( E. coli) sepsis in canines are related to insufficient host granulocyte colony-stimulating factor (G-CSF). Two-year-old purpose-bred beagles had intraperitoneal E. coli-infected or -noninfected fibrin clots surgically placed. By 10 to 12 h following clot, both infected survivors and nonsurvivors had marked increases ( P = 0.001) in serum G-CSF levels (mean peak G-CSF ng/ml ± SE, 1,931 ± 364 and 2,779 ± 681, respectively) compared with noninfected controls (134 ± 79), which decreased at 24 to 48 h. Despite increases in G-CSF, infected clot placement caused delayed ( P = 0.06) increases in PMN (mean ± SE change from baseline in cells × 103/mm3at 24 and 48 h) in survivors (+3.9 ± 3.9 and +13.8 ± 3.6) compared with noninfected controls (+13.1 ± 2.8 and +9.1 ± 2.5). Furthermore, infected nonsurvivors had decreases in PMN (−1.4 ± 1.0 and −1.1 ± 2.3, P = 0.006 compared with the other groups). We next investigated whether administration of G-CSF immediately after clot placement and continued for 96 h to produce more rapid and prolonged high levels of G-CSF after infection would alter PMN levels. Although G-CSF caused large increases in PMN compared with control protein from 2 to 48 h following clot in noninfected controls, it caused much smaller increases in infected survivors and decreases in infected nonsurvivors ( P = 0.03 for the ordered effect of G-CSF comparing the three groups). Thus insufficient host G-CSF is unlikely the cause of decreased circulating PMN in this canine model of sepsis. Other factors associated with sepsis either alone or in combination with G-CSF itself may reduce increases or cause decreases in circulating PMN.

Objective: Tumor necrosis factor (TNF) is an important mediator involved in the pathogenesis of sepsis. We review clinical studies investigating the efficacy of anti-TNF therapy in decreasing mortality rates in septic patients. Data Sources: We conducted a computerized bibliographic search of randomized, clinical, multicenter trials studying the effects of anti-TNF therapy in the treatment of sepsis. We included all primary studies, reviewed all published meta-analyses, and contacted primary investigators of multicenter trials where necessary. Data Synthesis: Almost all randomized studies targeting TNF during sepsis show a small, albeit nonsignificant, benefit in decreasing mortality. Strategies using monoclonal antibodies are more effective than are strategies using TNF receptor proteins. Analysis of randomized multicenter trials shows a small but significant benefit with anti-TNF therapeutic strategies. Furthermore, a recent study in 2634 septic patients using a murine anti-TNF antibody shows a 3.6% significant benefit in reducing mortality. Conclusions: Anti-TNF strategies are only partially effective in patients with sepsis. Although individual studies show small, nonsignificant benefits, analysis of all trial data as well as data from a recent trial in a large population of septic patients show that anti-TNF strategies may confer a small survival benefit. Better characterization of patients and a more multimodal approach by concomitantly targeting other mediators involved in sepsis may be helpful in enlarging the clinical benefit of anti-TNF therapy.

To study the effects of fucoidin on leukocyte rolling and emigration and bacterial colonization in a peritonitis sepsis model in rats.A controlled study in 64 male Wistar rats, anesthetized and rendered septic by cecal ligation and puncture (CLP). Immediately after CLP 32 animals received a continuous infusion of fucoidin and 32 a continuous infusion of Ringer's lactate.Systemic leukocyte counts were determined every 2 h after CLP. Surviving animals were anesthetized 24 h after CLP, and intravital measurements of leukocyte rolling in venules in the cremaster muscle were performed. The animals were then killed and their organs harvested for histological and microbiological examinations. The 24-h survival was comparable in the two groups. Fucoidin-treated animals had higher leukocyte counts in the systemic circulation and lower counts in the lungs, liver, abdominal cavity, and brain than control animals. The number of bacterial colony forming units in the abdominal cavity, lungs, liver, brain and blood did not differ in the two groups. Fucoidin treatment changed the type of bacteria predominantly found in the examined organs from Escherichia coli to Pseudomonas aeruginosa.In an intra-abdominal model of sepsis we found that treatment with fucoidin induces leukocytosis inhibits leukocyte rolling and reduces leukocyte emigration in the abdominal cavity, lungs, and liver. Reduction in the number of emigrating leukocytes was not associated with an increase in bacterial counts found in the examined organs.

Objectives To determine correlations and predictive strength of surrogate markers (body temperature, leukocyte count, C-reactive protein [CRP], and procalcitonin [PCT]) with elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in septic patients. Design Prospective consecutive case series. Setting Surgical intensive care unit (ICU) of a university hospital. Patients A total of 175 patients experiencing intensive care unit stays >48 hrs categorized for sepsis according to ACCP/ SCCM Consensus Conference criteria. Measurements and main results CRP and PCT were both significantly correlated with TNF-alpha and IL-6. Based on the area-under-the-curve of the receiver operating characteristics curves, predicting capability was highest for PCT (0.814 for TNF-alpha >40 pg/mL and 0.794 for IL-6 >500 pg/mL), moderate with CRP (0.732 and 0.716, respectively), and lowest for leukocyte count (0.493 and 0.483, respectively) and body temperature (0.587 and 0.589, respectively). Sensitivity, specificity, positive, and negative predictive values and test effectiveness all followed this same pattern of being highest for PCT followed by CRP, with leukocyte count and body temperature being lowest. Conclusion PCT may be an early and better marker of elevated cytokines than the more classic criteria of inflammation.

We investigated if bacteria type alters outcome with prophylactic granulocyte colony stimulating factor (G-CSF) therapy during pneumonia. Rats received G-CSF or placebo daily for 6 d and after the third dose were intrabronchially inoculated with either Escherichia coli or Staphylococcus aureus. Without G-CSF, E. coli and S. aureus produced similar (p = NS) mortality rates (36 versus 38%) and serial changes in mean circulating neutrophil counts (CNC), but differing mean (+/- SE) tumor necrosis factor (TNF) levels (E. coli, 259 +/- 104 versus S. aureus, 51 +/- 17 pg/ml, p = 0.01). G-CSF prior to bacteria increased mean CNC more than six times compared with placebo (p = 0.001). However, with G-CSF in the first 6 h after E. coli, there was a greater than 20-fold decrease in mean (+/- SE) CNC (x 10(3)/ mm3) to below placebo (0.5 +/- 0.1 versus 0.8 +/- 0.1), whereas with G-CSF after S. aureus, there was only a fivefold decrease in mean CNC and CNC were greater than placebo (1.8 +/- 0.2 versus 0.8 +/- 0.1) (E. coli versus S. aureus decrease in CNC with G-CSF, p = 0.001). With E. coli, G-CSF worsened oxygenation and increased bacteremia and mortality, whereas with S. aureus, G-CSF improved oxygenation and decreased bacteremia and mortality (G-CSF therapy, E. coli versus S. aureus, p = 0.03, 0.05, and 0.001, respectively). Thus, during S. aureus pneumonia with low TNF levels, G-CSF increased CNC and bacterial clearance, resulting in less pulmonary injury and decreased death. During E. coli pneumonia with high TNF levels, G-CSF paradoxically decreased CNC, resulting in impaired bacterial clearance and worsened pulmonary injury and death. Bacterial species and the associated inflammatory mediator response can alter outcome with prophylactic G-CSF therapy during pneumonia.

We investigated the effects of N(omega)-monomethyl-L-arginine (L-NMMA) and fluid loading on tumor necrosis factor (TNF)-induced cardiovascular dysfunction in awake dogs. L-NMMA (40 mg x kg(-1) given intravenously over a period of 10 min, and followed by dosing at 40 mg x kg(-1) x h(-1) for 6 h) and TNF (20 or 45 microg x kg(-1) given intravenously for 20 min), given alone or in combination, significantly decreased stroke volume, cardiac index, oxygen delivery, and left-ventricular (LV) function plots over a period of 6 h. Of note was that the cardiac-depressant effects of TNF and L-NMMA given together were significantly less than additive. Thus, the combination was beneficial (or significantly less harmful to cardiac performance than expected), possibly because L-NMMA augmented cardiac preload as shown by significant increases in both pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP). Fluid challenges at 6 h (Ringer's solution at 80 ml x kg(-1) given over a period of 30 min) also significantly increased PCWP and CVP, and abolished the beneficial preload effect of L-NMMA on cardiac performance. Thus, after fluid loading, the cardiac-depressant effects of TNF and L-NMMA given together became equal to the sum of those produced by TNF and L-NMMA given separately. Although L-NMMA significantly decreased serum nitrite/nitrate levels, TNF did not increase these end products of nitric oxide (NO) production relative to controls. Therefore, after preload abnormalities were eliminated with fluid loading, L-NMMA had no beneficial effect on TNF-induced cardiac depression, and TNF did not increase end products of NO production. These findings are not consistent with NO being the mechanism of TNF-induced acute cardiac depression.

Objective To compare total plasma antioxidant capacity and selected individual antioxidants in patients with varying degrees of severity of sepsis. Design A prospective, observational, consecutive case study. Setting A 16-bed intensive care unit (ICU) in a university teaching hospital. Interventions None. Patients Forty-six healthy controls, ten ICU patients, nine patients with systemic inflammatory response syndrome (SIRS), 11 septic patients, and 14 septic shock patients. Plasma was obtained in healthy patients scheduled for minor surgery immediately before anesthesia and in ICU patients within 24 hrs of admittance to the unit or diagnosis of SIRS, sepsis, or septic shock. Measurements and main results Using the total peroxyl radical trapping method, we found plasma antioxidant capacity to be lower in septic patients but higher in septic shock patients, as compared with controls. Bilirubin was the greatest contributor to the increase with shock, followed by uric acid. Neopterin also correlated with the peroxyl radical trapping antioxidant parameter values. Conclusion Although total plasma antioxidant capacity is decreased from normal levels in septic patients, an increase in some oxidants contributes to an increased total antioxidant capacity in septic shock patients.

Background Fiberoptic bronchoscopy has been recommended to verify the position of double-lumen tubes (DLT), but this remains controversial. The authors studied the role of bronchoscopy for placing and monitoring right- and left-sided DLTs after blind intubation and after positioning the patient. Methods Two hundred patients having thoracic surgery requiring DLT insertion were prospectively studied. "Blind" tracheal intubations were done with 163 left-sided and 37 right-sided disposable polyvinyl chloride Robertshaw tubes. Bronchoscopy was performed by a different anesthesiologist after intubation and conventional clinical verification of correct placement and after patient positioning for thoracotomy. A DLT was considered malpositioned when it had to be moved >0.5 cm to correct its position. Critical malpositions were those that might have affected patient safety or influenced the surgical procedure if left uncorrected. Results After "blind" DLT intubation, clinical evidence of malpositioning was found in 28 patients. This was confirmed by fiberoptic assessment. In 172 patients in whom placement was judged correct by clinical assessment, malpositioning was detected by bronchoscopy in 79 cases, 25 of which were critical. After patient positioning, DLTs were found to be displaced in 93 patients, 48 of which were critical. Right-sided DLTs were significantly more likely to be malpositioned than were left-sided DLTs. Two complications were related to unsatisfactory lung separation in the 200 patients studied. Conclusions After blind intubation and patient positioning, more than one third of DLTs required repositioning. Routine bronchoscopy is therefore recommended after intubation and after patient positioning.

Quezado, Zenaide M. N., Charles Natanson, Waheedullah Karzai, Robert L. Danner, Cezar A. Koev, Yvonne Fitz, Donald P. Dolan, Steven Richmond, Steven M. Banks, Laura Wilson, and Peter Q. Eichacker.Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis. J. Appl. Physiol. 84(1): 107–115, 1998.—We investigated the effect of inhaled nitric oxide (NO) at increasing fractional inspired O2concentrations ([Formula: see text]) on hemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious, spontaneously breathing, tracheotomized 2-yr-old beagles had intrabronchial inoculation with either 0.75 or 1.5 × 1010 colony-forming units/kg of E. coli 0111:B4 (infected) or 0.9% saline (noninfected) in one or four pulmonary lobes. We found that neither the severity nor distribution (lobar vs. diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasing[Formula: see text] (0.08, 0.21, 0.50, and 0.85), NO (80 parts/million) progressively increased arterial[Formula: see text] [−0.3 ± 0.6, 3 ± 1, 13 ± 4, 10 ± 9 (mean ± SE) Torr, respectively] and decreased the mean arterial-alveolar O2 gradient (0.5 ± 0.3, 4 ± 2, −8 ± 7, −10 ± 9 Torr, respectively). In contrast, in noninfected animals, the effect of NO was significantly different and opposite; NO progressively decreased mean[Formula: see text] with increasing[Formula: see text] (2 ± 1, −5 ± 3, −2 ± 3, and −12 ± 5 Torr, respectively; P < 0.05 compared with infected animals) and increased mean arterial-alveolar O2 gradient (0.3 ± 0.04, 2 ± 2, 1 ± 3, 11 ± 5 Torr; P< 0.05 compared with infected animals). In normal and infected animals alike, only at [Formula: see text]≤0.21 did NO significantly lower mean pulmonary artery pressure, pulmonary artery occlusion pressure, and pulmonary vascular resistance index (all P < 0.01). However, inhaled NO had no significant effect on increases in mean pulmonay artery pressure associated with bacterial pneumonia. Thus, during bacterial pneumonia, inhaled NO had only modest effects on oxygenation dependent on high[Formula: see text] and did not affect sepsis-induced pulmonary hypertension. These data do not support a role for inhaled NO in bacterial pneumonia. Further studies are necessary to determine whether, in combination with ventilatory support, NO may have more pronounced effects.

The effects of a rapid increase in inspired desflurane concentration on systemic haemodynamics and plasma catecholamines were studied in seven pigs (22-30 kg). Following premedication (flunitrazepam 0.4 mg/kg i.m.), anaesthesia was induced (propofol 2.5 mg/kg i.v., vecuronium 0.2 mg/kg i.v.), the trachea orally intubated, and ventilation controlled. Anaesthesia was maintained with N2O/O2 (70%/30%), propofol (50 μg/kg/min), desflurane 12% end-tidal concentration), and vecuronium (0.3 mg/kg/h). After cannulation of both femoral arteries for subsequent simultaneous systemic pressure measurements and blood sampling for determination of epinephrine (E) and norepinephrine (NE) plasma levels, N2O and propofol were discontinued, and FiO2 and end-tidal concentration of desflurane increased to >0.9 and 3%, respectively. Forty minutes later, the inspired concentration of desflurane was abruptly increased to 15%. Mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of E and NE were determined before and 1, 2, 4, 8, 16, and 32 min after increasing the desflurane concentration. Plasma concentrations of E and NE were determined by high performance liquid chromatography (HPLC) with electrochemical detection. Data were analysed by repeated measures ANOVA (significance level P

We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.

60 patients, ASA I-III, underwent one-lung ventilation for open or video-assisted thoracic surgery randomized either with intravenous anesthesia with propofol or with inhalational anesthesia with 1 MAC sevoflurane. Propofol was titrated during one-lung ventilation to achieve a mean arterial pressure of 75-80 mmHg. Blood gas analyses, hemodynamic and respiratory parameters were measured during two-lung ventilation at the beginning of the surgical procedure and 10 min, 20 min and 30 min after start of one-lung ventilation. At all time points, hemodynamic and respiratory parameters were comparable in both groups. Oxygenation did not differ between groups at comparable mean arterial blood pressures.

When switching from two-lung to one-lung ventilation (OLV), shunt fraction increases, oxygenation is impaired, and hypoxemia may occur. Hypoxemia during OLV may be predicted from measurements of lung function, distribution of perfusion between the lungs, whether the right or the left lung is ventilated, and whether the operation will be performed in the supine or in the lateral decubitus position. Hypoxemia during OLV may be prevented by applying a ventilation strategy that avoids alveolar collapse while minimally impairing perfusion of the dependent lung. Choice of anesthesia does not influence oxygenation during clinical OLV. Hypoxemia during OLV may be treated symptomatically by increasing inspired fraction of oxygen, by ventilating, or by using continuous positive airway pressure in the nonventilated lung. Hypoxemia during OLV may be treated causally by correcting the position of the double-lumen tube, clearing the main bronchi of the ventilated lung from secretions, and improving the ventilation strategy.

During one-lung ventilation (OLV), hypoxic pulmonary vasoconstriction reduces venous admixture and attenuates the decrease in arterial O2 tension by diverting blood from the nonventilated to the ventilated lung. In vitro, increasing concentrations of desflurane depresses hypoxic pulmonary vasoconstriction in a dose-dependent manner. Accordingly, we investigated the effects of increasing concentrations of desflurane on oxygenation during OLV in vivo. Thirteen pigs (25-30 kg) were anesthetized (induction: propofol 2-3 mg/kg IV; maintenance: N2 O/O2 50%/50%, desflurane 3%, propofol 50 [micro sign]g [middle dot] kg-1 [middle dot] min-1, and vecuronium 0.2 mg [middle dot] kg-1 [middle dot] h-1 IV), orotracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a left-sided, 28F, double-lumen tube was placed via tracheotomy. After double-lumen tube placement, N2 O and desflurane were discontinued, propofol was increased to 200 [micro sign]g [middle dot] kg-1 [middle dot] min-1, and the fraction of inspired oxygen was adjusted at 0.8. Anesthesia was then continued in random order with desflurane 5%, 10%, or 15% end-tidal concentrations while propofol was discontinued. Whereas mixed venous PO2, mean arterial pressure, cardiac output, and shunt fraction decreased in a dose-dependent manner, PaO2 remained unchanged with increasing concentrations of desflurane during OLV. These findings indicate that, in vivo, increasing concentrations of desflurane do not necessarily worsen oxygenation during OLV. Implications: Oxygenation during one-lung ventilation depends on reflex vasoconstriction in the nonventilated lung. In vitro, desflurane inhibits this reflex dose-dependently. Our results indicate that, in vivo, this does not necessarily translate to dose-dependent decreases in oxygenation during one-lung ventilation. (Anesth Analg 1999;89:215-7)

Objectives: Cardiopulmonary bypass (CPB) can be successfully performed in patients on hemodialysis. However, ischemic complications occur more often in these patients. This could partly be because of shunting through the arteriovenous (AV) fistula during CPB, resulting in reduced peripheral flow and oxygen (O2) delivery. Inadequate oxygen delivery during CPB should be reflected in a lower oxygen consumption (VO2) compared with patients without an AV fistula. Design: To test the hypothesis, the authors analyzed VO2 in three groups of patients retrospectively. Group 1 included 14 patients with end-stage renal failure (creatinine level 9.1 ± 0.3 mg/dL, urea level 126 ± 8 mg/dL) requiring hemodialysis through an AV fistula. Group 2 included 13 patients with compensated renal insufficiency (creatinine level 3.1 ± 0.4 mg/dL, urea level 106 ± 10 mg/dL) without an AV fistula. Group 3 included 14 patients with normal renal function (creatinine level 1.0 ± 0.1 mg/dL, urea level 44 ± 4 mg/dL). Setting: An operating room of a university hospital. Participants: Patients undergoing cardiac surgery requiring CPB. Measurements and Main Results: VO2 was calculated from the recorded hemodynamic and blood gas data using standard formulae. Data were analyzed using a two-way analysis of variance with a repeated measurement on one factor. Before undergoing CPB, VO2 was similar in all three groups. VO2 decreased in all three groups during hypothermic CPB (standard flow rate 2.2 L/min/m2, standard temperature 29°C) and returned to prebypass levels during rewarming. There was no difference in VO2 among the three groups during hypothermic CPB or during rewarming. Only base excess decreased more in group 1 patients compared with the other groups (p Conclusion: During hypothermic CPB at a flow rate of 2.2 L/min/m2, shunting through an AV fistula is unlikely to lead to decreased VO2 in dialysis patients.

Mechanical ventilation (MV) with large tidal volumes (V(T)) causes ventilator induced lung injury. Whereas immediate effects of short-term injurious ventilation are well studied, little is known about its long-term effects. We aimed to establish an animal model of selective injurious MV, permitting assessment of the long-term course of ventilation-induced lung injury. In anesthetized and instrumented rats (n = 26), laryngoscopy was performed, and one cannula for MV was placed in the left main bronchus and a second one in the trachea. Two ventilators were used to ventilate the left lung with high (20 mL/kg) and the right lung with low (4 mL/kg) V(T). In control animals, both lungs received low V(T). After 2 h of MV, animals were extubated and observed for 24 h and then killed. Left and right lungs were excised and sampled for further investigations. Survival in animals ventilated with the high V(T) was 90%. Twenty-four hours after MV, alveolar levels of humoral (tumor necrosis factor alpha, interleukin 6) and cellular (polymorphonuclear leukocytes) inflammatory markers were increased, and histological alterations were present in lungs ventilated with high V(T). A delayed decrease in PaO2 was noted 24 h after MV, with high V(T) delivered to one lung as compared with low V(T) delivered to both lungs. This animal model permits assessment of the long-term course of ventilation-induced lung injury and shows that pulmonary inflammation and histological alterations are present 24 h after unilateral injurious ventilation.

Erkrankungen des Herz-Kreislauf-Systems, die zu relevanten perioperativen Problemen fuhren konnen, sind arterielle Hypertonie, koronare Herzkrankheit, Herzklappenerkrankungen, Herzinsuffizienz und Herzrhythmusstorungen. Die Beurteilung sollte immer in Anbetracht des Schweregrades der Erkrankung und der Art und der Grose des operativen Eingriffs erfolgen. Eine hohe Qualitat der Behandlung zeichnet sich nicht allein durch die intraoperative Narkosefuhrung aus (vgl. ▸ Kap. 35), sondern durch die optimale praoperative Vorbereitung und die Pravention bzw. prompte Behandlung postoperativer Probleme.

In clinical lung injury areas of inflammation and structural alveolar alteration are unevenly distributed and interspaced between healthy or less injured lung areas. Positive end-expiratory pressure (PEEP) applied with mechanical ventilation (MV) may affect injured and healthy lung areas differently. We compared the effects of PEEP on the inflammatory response in injured and noninjured regions of the lung in an animal model of unilateral lung acid instillation. Anesthetized, paralyzed, and ventilated rats. Rats underwent left-endobronchial instillation with either hydrochloric acid or isotonic saline and were randomized 24 h later to MV using constant tidal volume (16 ml/kg) with either ZEEP, PEEP at 5 mmHg, or PEEP at 10 mmHg. After 4 h of MV the animals (n = 9 or 10 per group) were killed and inflammatory markers assessed in left- and right-lung lavage fluid samples. In four additional animals per group differential lung perfusion was assessed. Unilateral acid injury alone worsened oxygenation, decreased left-lung perfusion, and increased left-lung lavage neutrophil and macrophage counts and cytokine levels. MV with ZEEP further impaired oxygenation and further decreased left-lung perfusion in acid-injured animals. MV with high PEEP preserved oxygenation and significantly decreased left-lung lavage protein content and cell counts in acid-injured animals and had no deleterious effect on the right (noninjured) lung. In this model of unilateral lung acid injury high PEEP attenuates the inflammatory cell response in the acid-injured lung, preserved oxygenation and has no deleterious effects in the opposite lung.

The application of percutaneous transtracheal jet ventilation for emergency ventilation depends on special equipment which is often not available outside the operating room. The oxygen flow modulator is a new specially designed device for emergency ventilation using a low pressure oxygen supply. We studied the effects of the new device in comparison with a hand triggered emergency jet injector on oxygenation and ventilation in six pigs (21±1 kg). The animals were anaesthetized, tracheally intubated, and mechanically ventilated. Following central venous and pulmonary artery catheterization, a Paratrend 7 sensor was placed in the left femoral artery for continuous measurements of PaO 2 and PaCO 2 . Then an emergency transtracheal airway catheter was inserted into the trachea after surgical exposure. In randomized order each animal was ventilated via the transtracheal airway catheter with the hand triggered emergency jet injector (inspiratory/expiratory ( I / E ) ratio of 1:1; respiratory rate of 60 min −1 ; driving pressure 1.5 bar; FjetO 2 1.0) and the oxygen flow modulator (FiO 2 1.0 at an oxygen flow of 15 l min −1 ; respiratory rate of 60 min −1 ; I / E ratio of approximately 1:1) for 15 min each. After each phase of the experiment respiratory and hemodynamic variables were measured. Whereas PaO 2 was not significantly different between the two devices, PaCO 2 was higher during the hand-triggered jet ventilation. Thus, the efficacy of the oxygen flow modulator during the experiment was comparable with the efficacy of the hand triggered emergency jet injector.

UNLABELLED In a previous study we have shown that the antihypertensive drug, urapidil, stops postanesthetic shivering. One possible mechanism in the inhibition of postanesthetic shivering by urapidil may be alterations in thermoregulatory thresholds. We therefore studied the effects of urapidil on vasoconstriction and shivering thresholds during cold-induced shivering in volunteers. Seven healthy male volunteers were cooled by an infusion of saline at 4 degrees C on two study days separated by 48 h. Thermoregulatory vasoconstriction was estimated using forearm minus fingertip skin-temperature gradients, and values exceeding 0 degrees C were considered to represent significant vasoconstriction. The rectal core temperatures at the beginning of shivering and at vasoconstriction were considered the thermoregulatory thresholds. Before cooling, either 25 mg of urapidil or placebo was administered randomly and blindly to each volunteer. When shivering occurred continuously for 10 min, another 25 mg of urapidil was administered IV to completely stop shivering. Urapidil led to a decrease in core temperature at vasoconstriction and shivering threshold by 0.4 degrees C plus/minus 0.2 degrees C (P < 0.001) and 0.5 degrees C plus/minus 0.3 degrees C (P < 0.01), respectively. Oxygen consumption increased during shivering by 70% plus/minus 30% (P < 0.01) in comparison with baseline and decreased levels after shivering stopped, despite the continued low core temperature. Our investigation shows that urapidil stops postanesthetic shivering by decreasing important thermoregulatory thresholds. This means that shivering, not hypothermia, is treated, and hypothermia will need more attention in the postanesthesia care unit. IMPLICATIONS In this study we show that the antihypertensive drug urapidil stops cold-induced shivering and decreases normal thermoregulatory responses, i.e., the thresholds for vasoconstriction and shivering, in awake volunteers.