Trends in perioperative practices of high-risk surgical patients over a 10-year interval.

INTRODUCTION: In Brazil, data show an important decrease in morbi-mortality of high-risk surgical patients over a 10-year high. The objective of this post-hoc study was to evaluate the mechanism explaining this trend in high-risk surgical patients admitted to Brazilian ICUs in two large Brazilian multicenter cohort studies performed 10 years apart. METHODS: The patients included in the 2 cohorts studies published in 2008 and 2018 were compared after a (1:1) propensity score matching. Patients included were adults who underwent surgeries and admitted to the ICU afterwards. RESULTS: After matching, 704 patients were analyzed. Compared to the 2018 cohort, 2008 cohort had more postoperative infections (OR 13.4; 95%CI 6.1-29.3) and cardiovascular complications (OR 1.5; 95%CI 1.0-2.2), as well as a lower survival ICU stay (HR = 2.39, 95% CI: 1.36-4.20) and hospital stay (HR = 1.64, 95% CI: 1.03-2.62). In addition, by verifying factors strongly associated with hospital mortality, it was found that the risk of death correlated with higher intraoperative fluid balance (OR = 1.03, 95% CI 1.01-1.06), higher creatinine (OR = 1.31, 95% CI 1.1-1.56), and intraoperative blood transfusion (OR = 2.32, 95% CI 1.35-4.0). By increasing the mean arterial pressure, according to the limits of sample values from 43 mmHg to 118 mmHg, the risk of death decreased (OR = 0.97, 95% CI 0.95-0.98). The 2008 cohort had higher fluid balance, postoperative creatinine, and volume of intraoperative blood transfused and lower mean blood pressure at ICU admission and temperature at the end of surgery. CONCLUSION: In this sample of ICUs in Brazil, high-risk surgical patients still have a high rate of complications, but with improvement over a period of 10 years. There were changes in the management of these patients over time.

Intraoperative fluid balance and cardiac surgery-associated acute kidney injury: a multicenter prospective study

Abstract Background Recent data suggest the regime of fluid therapy intraoperatively in patients undergoing major surgeries may interfere in patient outcomes. The development of postoperative Acute Kidney Injury (AKI) has been associated with both Restrictive Fluid Balance (RFB) and Liberal Fluid Balance (LFB) during non-cardiac surgery. In patients undergoing cardiac surgery, this influence remains unclear. The study objective was to evaluate the relationship between intraoperative RFB vs. LFB and the incidence of Cardiac-Surgery-Associated AKI (CSA-AKI) and major postoperative outcomes in patients undergoing on-pump Coronary Artery Bypass Grafting (CABG). Methods This prospective, multicenter, observational cohort study was set at two high-complexity university hospitals in Brazil. Adult patients who required postoperative intensive care after undergoing elective on-pump CABG were allocated to two groups according to their intraoperative fluid strategy (RFB or LFB) with no intervention. Results The primary endpoint was CSA-AKI. The secondary outcomes were in-hospital mortality, cardiovascular complications, ICU Length of Stay (ICU-LOS), and Hospital LOS (H-LOS). After propensity score matching, 180 patients remained in each group. There was no difference in risk of CSA-AKI between the two groups (RR = 1.15; 95% CI, 0.85-1.56, p= 0.36). The in-hospital mortality, H-LOS and cardiovascular complications were higher in the LFB group. ICU-LOS was not significantly different between the two groups. ROCcurve analysis determined a fluid balance above 2500 mL to accurately predict in-hospital mortality. Conclusion Patients undergoing on-pump CABG with LFB when compared with patients with RFB present similar CSA-AKI rates and ICU-LOS, but higher in-hospital mortality, cardiovascular complications, and H-LOS.

Intraoperative fluid balance and cardiac surgery-associated acute kidney injury: a multicenter prospective study.

BACKGROUND: Recent data suggest the regime of fluid therapy intraoperatively in patients undergoing major surgeries may interfere in patient outcomes. The development of postoperative Acute Kidney Injury (AKI) has been associated with both Restrictive Fluid Balance (RFB) and Liberal Fluid Balance (LFB) during non-cardiac surgery. In patients undergoing cardiac surgery, this influence remains unclear. The study objective was to evaluate the relationship between intraoperative RFB vs. LFB and the incidence of Cardiac-Surgery-Associated AKI (CSA-AKI) and major postoperative outcomes in patients undergoing on-pump Coronary Artery Bypass Grafting (CABG). METHODS: This prospective, multicenter, observational cohort study was set at two high-complexity university hospitals in Brazil. Adult patients who required postoperative intensive care after undergoing elective on-pump CABG were allocated to two groups according to their intraoperative fluid strategy (RFB or LFB) with no intervention. RESULTS: The primary endpoint was CSA-AKI. The secondary outcomes were in-hospital mortality, cardiovascular complications, ICU Length of Stay (ICU-LOS), and Hospital LOS (H-LOS). After propensity score matching, 180 patients remained in each group. There was no difference in risk of CSA-AKI between the two groups (RR = 1.15; 95% CI, 0.85-1.56, p = 0.36). The in-hospital mortality, H-LOS and cardiovascular complications were higher in the LFB group. ICU-LOS was not significantly different between the two groups. ROCcurve analysis determined a fluid balance above 2500 mL to accurately predict in-hospital mortality. CONCLUSION: Patients undergoing on-pump CABG with LFB when compared with patients with RFB present similar CSA-AKI rates and ICU-LOS, but higher in-hospital mortality, cardiovascular complications, and H-LOS.

The effects of vasopressors with and without dobutamine on haemodynamics, metabolism and gut injury during endotoxic shock in rabbits. A controlled study.

INTRODUCTION: Vasopressors increase arterial pressure but they may have deleterious effects on mesenteric blood flow. We aimed to evaluate the response of gut biomarkers and superior mesenteric blood flow to different vasopressors with and without dobutamine. MATERIAL AND METHODS: Thirty New Zealand rabbits were included and randomly allocated to 5 groups: group A - sham group; group B - norepinephrine; group C - norepinephrine plus dobutamine; group D - vasopressin; and group E - vasopressin plus dobutamine. Mean arterial pressure (MAP) target was greater than 60 mmHg. Endotoxic shock was induced by intra-venous injection of lipopolysaccharide (LPS) in four of the five groups. Aortic blood flow (Qao), superior mesenteric artery flow (QSMA) and lactate were measured after LPS injection. Enterocyte damage was evaluated by measurements of serum citrulline and intestinal fatty acid-binding protein (I-FABP) after 4 h. RESULTS: The largest reduction in Qao occurred in group D (64 ± 17.3 to 38 ± 7.5 mL min-1; P = 0.04). QSMA also declined significantly in groups D and E and remained lower than in the other groups over 4 h (group D - baseline: 65 ± 31; 1 h: 37 ± 10; 2 h: 38 ± 10; 3 h: 46 ± 26; and 4 h: 48 ± 15 mL min-1; P < 0.005; group E - baseline: 73 ± 14; 1 h: 28 ± 4.0; 2 h: 37 ± 6.4; 3 h: 40 ± 11; and 4 h: 48 ± 11; P < 0.005; all in mL min-1). Serum citrulline was significantly lower in groups D (P = 0.014) and E (P = 0.019) in comparison to group A. The fluid administration regimen was similar in all groups. CONCLUSIONS: Vasopressin seems to negatively impact gut enterocyte function during endotoxic shock despite the association of an inodilator and adequate fluid replacement.

The effects of acute kidney injury in a multicenter cohort of high-risk surgical patients.

BACKGROUND AND OBJECTIVES: Patients who develop post-operative acute kidney injury (AKI) have a poor prognosis, especially when undergoing high-risk surgery. Therefore, the objective of this study was to evaluate the outcome of patients with AKI acquired after non-cardiac surgery and the possible risk factors for this complication. METHODS: A multicenter, prospective cohort study with patients admitted to intensive care units (ICUs) after non-cardiac surgery was conducted to assess whether they developed AKI. The patients who developed AKI were then compared to non-AKI patients. RESULTS: A total of 29 ICUs participated, of which 904 high-risk surgical patients were involved in the study. The occurrence of AKI in the post-operative period was 15.8%, and the mortality rate of post-operative AKI patients at 28 days was 27.6%. AKI was strongly associated with 28-day mortality (OR = 2.91; 95% CI 1.51-5.62; p = 0.001), and a higher length of ICU and hospital stay (p < 0.001). Independent factors for the risk of developing AKI were pre-operative anemia (OR = 7.01; 95% CI 1.69-29.07), elective surgery (OR = 0.45; 95% CI 0.21-0.97), SAPS 3 (OR = 1.04; 95% CI 1.02-1.06), post-operative vasopressor use (OR = 2.47; 95% CI 1.34-4.55), post-operative infection (OR = 8.82; 95% CI 2.43-32.05) and the need for reoperation (OR= 7.15; 95% CI 2.58-19.79). CONCLUSION: AKI was associated with the risk of death in surgical patients and those with anemia before surgery, who had a higher SAPS 3, needed a post-operative vasopressor, or had a post-operative infection or needed reoperation were more likely to develop AKI post-operatively.

Peripheral muscular ultrasound as outcome assessment tool in critically ill patients on mechanical ventilation: An observational cohort study.

BACKGROUND & AIMS: Survivors of critical illness experience significant skeletal muscle wasting that may predict clinical outcome. Ultrasound (US) is a noninvasive method that can measure muscle quadriceps muscle layer thickness (QMLT) at the bedside. The aim of this study was to determine the muscle loss assessed by ultrasonography (US) of the quadriceps femoris muscle in critically ill patients on mechanical ventilation and its relationship with hospital outcomes. METHODS: This study involved patients ≥18 years admitted to the intensive care unit who needed mechanical ventilation for at least 48 h. The quadriceps muscle layer thickness (QMLT) in the two-thirds of the thigh was quantified using bedside US. The QMLT of the left and right legs on the first (D1), third (D3), and seventh (D7) days were measured. RESULTS: US quadriceps thickness measurements were performed in 74 critically ill patients. The mean age was 62.3 ± 19.5 years, 54.1% of the patients were men, with a BMI of 25.5 ± 4.6 kg/m2, SAPS 3 of 55.2 ± 17.2, and NRS of 3.2 ± 1.0. The percentage muscle thickness declined at the right leg in 15% (95%CI, 10.5%-19.4%), and 12.7% (95%CI, 9.1%-16.3%) at the left leg from the first to the seventh day. Receiver operating characteristic showed cutoff value in muscle thickness of ≤1.64 cm on day 7 could predict survival (area under then curve = 0.7; 95% CI, 0.582-0.801). In Cox regression after adjusting, the probability of patients remaining on mechanical ventilation was higher with ≤1.64 cm loss of thigh muscle thickness on day 7; HR = 2.1 (95% CI 1.1-3.8, P = 0.017). The same occurred about ICU survival probability; HR = 3.7 (95% CI 1.2 to 11.5) and hospital survival probability; HR = 4.5 (95% CI 1.5 to 13.7). CONCLUSIONS: The measurement of QMLT using US showed that critically ill patients on mechanical ventilation presented with muscle wasting and greater loss of muscle thickness was associated with worse outcomes.

Intensive care management of patients with COVID-19: a practical approach.

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic facing humanity since the Spanish flu pandemic in the early twentieth century. Since there is no specific antiviral treatment, optimized support is the most relevant factor in the patient's prognosis. In the hospital setting, the identification of high-risk patients for clinical deterioration is essential to ensure access to intensive treatment of severe conditions in a timely manner. The initial management of hypoxemia includes conventional oxygen therapy, high-flow nasal canula oxygen, and non-invasive ventilation. For patients requiring invasive mechanical ventilation, lung-protective ventilation with low tidal volumes and plateau pressure is recommended. Cardiovascular complications are frequent and include myocardial injury, thrombotic events, myocarditis, and cardiogenic shock. Acute renal failure is a common complication and is a marker of poor prognosis, with significant impact in costs and resources allocation. Regarding promising therapies for COVID-19, the most promising drugs until now are remdesivir and corticosteroids although further studies may be needed to confirm their effectiveness. Other therapies such as, tocilizumab, anakinra, other anti-cytokine drugs, and heparin are being tested in clinical trials. Thousands of physicians are living a scenario that none of us have ever seen: demand for hospital exceed capacity in most countries. Until now, the certainty we have is that we should try to decrease the number of infected patients and that an optimized critical care support is the best strategy to improve patient's survival.

Worsening of heart failure by coronavirus disease 2019 is associated with high mortality.

AIMS: Patients with advanced heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and concurrent coronavirus disease 2019 (COVID-19) might have a higher risk of severe events. METHODS AND RESULTS: We retrospectively studied 16 patients with advanced HFrEF who developed COVID-19 between 1 March and 29 May 2020. Follow-up lasted until 30 September. Ten patients previously hospitalized with decompensated HFrEF were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during hospitalization. Six patients undergoing ambulatory care at initiation of COVID-19 symptoms were hospitalized because of advanced HFrEF. All patients who experienced worsening of HFrEF due to COVID-19 required higher doses or introduction of additional inotropic drugs or intra-aortic balloon pump in the intensive care unit. The mean intravenous dobutamine dose before SARS-CoV-2 infection in previously hospitalized patients (n = 10) and the median (inter-quartile range) peak intravenous dobutamine dose during SARS-CoV-2 infection in all patients (n = 16) were 2 (0-7) µg/kg/min and 20 (14-20) (P < 0.001), respectively. During follow-up, 56% underwent heart transplantation (n = 2) or died (n = 7). Four patients died during hospitalization from mixed shock consequent to severe acute respiratory syndrome with inflammatory storm syndrome associated with septic and cardiogenic shock during COVID-19. After COVID-19 recovery, two patients died from mixed septic and cardiogenic shock and one from sustained ventricular tachycardia and cardiogenic shock. Five patients were discharged from hospital to ambulatory care. Four were awaiting heart transplantation. CONCLUSION: Worsening of advanced HF by COVID-19 is associated with high mortality. This report highlights the importance of preventing COVID-19 in patients with advanced HF.

Evaluation of Urinary NGAL as a Diagnostic Tool for Acute Kidney Injury in Critically Ill Patients With Infection: An Original Study.

BACKGROUND: Acute kidney injury (AKI) is a common complication in critical care patients. The presence of AKI is a marker for poor outcomes such as longer hospitalization durations, more hospital readmissions, and especially, higher mortality rates. Sepsis is one of the major causes of AKI within the intensive care unit (ICU) population. Sepsis-related AKI occurs in approximately 20% of patients, reaching more than 50% in patients with septic shock. The diagnosis of AKI depends on urine output and/or serum creatinine measurements. Unfortunately, serum creatinine is a late and unreliable (insensitive and nonspecific) indicator of AKI. However, biomarkers of renal damage have great potential in facilitating early diagnosis of AKI. Several biomarkers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL), have been used in the early detection of AKI. OBJECTIVES: The aim of this study was to evaluate uNGAL for the diagnosis and prognosis of AKI in critical ill patients with infections. DESIGN: Original study (Cohort Prospective Observational). SETTING: Study in 2 ICUs of different Brazilian hospitals, in the city of Curitiba: Hospital de Clínicas da Universidade Federal do Paraná and Hospital da Polícia Militar do Paraná, from November 12, 2016 to May 15, 2018. PARTICIPANTS: Critically ill patients with infections, sepsis, or septic shock were selected. The inclusion criteria were patients older than 18 years with infection. They were followed up for 30 days in the analysis of outcomes. We requested that consent forms be signed by all eligible patients or their caregivers. MEASUREMENTS: The urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels of the patients were measured on 4 consecutive days and was assayed using a chemiluminescent microparticle immunoassay system. The screening time occurred within 72 hours of admission to the ICU. The first urine sample was collected within the first 24 hours of the screening hours. Mortality and AKI were assessed during first 30 days. METHODS: clinical and laboratory data, including daily uNGAL levels, were assessed. The AKI stage using the KDIGO criteria was evaluated. Sensitivity, specificity, and the area under the curve-receiver operating characteristic (AUC-ROC) values were calculated to determine the optimal uNGAL level for predicting AKI. RESULTS: We had 38 patients who completed the study during the screening period. The incidence of AKI was 76.3%. The hospitalization period was longer in the group that developed AKI, with 21 days of median (interquartile range [IQR]: 13.5-25); non-AKI group had a median of 13 days (IQR 7-18; P = .019). We found a direct relationship between uNGAL levels and the progression to AKI. Increased values of the biomarker were associated with the worsening of AKI (P < .05). The cutoff levels of uNGAL that identified patients who would progress to AKI were the following: (d1) >116 ng/mL, (d2) >100 ng/mL, and (d3) 284 ng/mL. The value of the fourth and last measurement was not predictive of patients who would progress to AKI. The median urinary uNGAL was also associated with mortality on Days 1, 3, and 4: d1, P = .039; d3, P = .005; d4, P = .005. The performance of uNGAL in detecting AKI patients (AUC-ROC = 0.881). There were no risk factors other than AKI that could be correlated with increased uNGAL levels on Day 1. LIMITATIONS: The study was carried out in 2 centers, having used only 1 biomarker, and our small number of patients were limitations. CONCLUSION: the uNGAL had an association in its values with the diagnosis and prognosis of patients with severe infections and AKI. We suggest that studies with a greater number of patients could better establish the cutoff values of uNGAL and/or serum NGAL in the identification of infected patients who are at a high risk of developing AKI.

CONTEXTE`: L'insuffisance rénale aiguë (IRA) est une complication fréquente chez les patients des unités de soins intensifs (USI). L'IRA est un marqueur d'issues défavorables pour ces patients, notamment d'hospitalisations plus longues, de réadmissions plus fréquentes et surtout, de taux de mortalité plus élevés. Le sepsis est une des principales causes d'IRA chez les patients soignés aux USI; cette infection liée à l'IRA survient chez environ 20 % des patients et peut toucher plus de 50 % des patients en choc septique. Le diagnostic de l'IRA repose sur la mesure de la diurèse ou du taux de créatinine sérique; cette dernière mesure s'avérant toutefois un indicateur tardif et peu fiable (non spécifique et peu sensible). Les biomarqueurs d'une lésion rénale pourraient potentiellement faciliter un diagnostic précoce de la maladie. Plusieurs, dont la NGAL urinaire ou uNGAL (urinary neutrophil gelatinase-associated lipocalin) ont déjà été utilisés dans ce contexte. OBJECTIFS: Évaluer le potentiel de la uNGAL pour le diagnostic et le pronostic de l'IRA chez les patients gravement malades souffrant d'infections. TYPE D'ÉTUDE: Étude initiale (étude de cohorte prospective et observationnelle). CADRE: L'étude s'est tenue entre le 12 novembre 2016 et le 15 mai 2018 dans les USI de deux hôpitaux de Curitiba au Brésil (Hospital de Clínicas da Universidade Federal do Paraná et Hospital da Polícia Militar do Paraná). SUJETS: Les patients adultes, gravement malades et atteints d'une infection, d'un sepsis ou d'un choc septique ont été retenus. Le consentement écrit de tous les patients admissibles et de leurs représentants était exigé. Les sujets ont été suivis pendant 30 jours pour l'analyse des résultats. MESURES: Les taux d'uNGAL ont été mesurés pendant quatre jours consécutifs et analysés par immunodosage microparticulaire par chimiluminescence. Le dépistage a eu lieu dans les 72 heures suivant l'admission aux USI et le premier échantillon d'urine a été prélevé dans les 24 premières heures de la période de dépistage. L'IRA et la mortalité ont été évaluées pendant les 30 premiers jours. MÉTHODOLOGIE: L'analyse porte sur les données cliniques et de laboratoire, y compris les taux quotidiens d'uNGAL. Le stade de l'IRA a été établi selon les critères KDIGO. La sensibilité, la spécificité et les valeurs de surface sous la courbe ROC (SSC-ROC) ont servi à calculer le taux optimal d'uNGAL prédictif de l'IRA. RÉSULTATS: L'incidence de l'IRA s'établissait à 76,3 % parmi les 38 patients ayant complété le dépistage. Les patients souffrant d'IRA étaient hospitalisés plus longtemps que les autres (durée médiane: 21 jours [ÉIQ: 13,5-25] contre 13 jours [ÉIQ: 7-18] pour les autres patients; p=0,019). Un lien direct entre le taux d'uNGAL et une progression vers l'IRA a été observé, et l'augmentation de ces valeurs a été associée à une aggravation de l'IRA (p<0,05). Les valeurs seuil d'uNGAL permettant de diagnostiquer une évolution vers l'IRA étaient les suivantes: (j1) > 116 ng/mL; (j2) > 100 ng/mL et (j3) 284 ng/mL. La valeur de la 4e et dernière mesure n'a pas permis de prédire une évolution vers l'IRA. Les taux médians d'uNGAL ont également été associés à la mortalité aux jours 1,3 et 4; avec des valeurs de p s'établissant à 0,039 (j1), 0,005 (j3) et 0,005 (j4). La performance du taux d'uNGAL pour détecter l'IRA (SSC-ROC) était de 0,881. Aucun facteur de risque autre que l'IRA n'a pu être corrélé avec une augmentation du taux d'uNGAL au jour 1. LIMITES: L'étude ne s'est tenue que dans deux centres, sur un échantillon restreint de patients, et ne portait que sur un seul biomarqueur. CONCLUSION: Le taux d'uNGAL a montré une association avec le diagnostic et le pronostic des patients souffrant d'infections graves et d'IRA. Nous pensons que des études sur un plus grand nombre de patients pourraient préciser les valeurs seuil d'uNGAL ou de NGAL sérique pour le dépistage des patients infectés qui présentent un risque élevé de développer une IRA.

Comparative Analysis of the Collapsibility Index and Distensibility Index of the Inferior Vena Cava Through Echocardiography with Pulse Pressure Variation That Predicts Fluid Responsiveness in Surgical Patients: An Observational Controlled Trial.

OBJECTIVE: The objective for the present study was to compare the collapsibility (IcIVC) and distensibility (IdIVC) indices of the inferior vena cava with pulse pressure variation (PPV) and determine the accuracy and cutoff points of IcIVC and IdIVC that best predict response to intravenous fluid therapy in surgical patients. DESIGN: Observational, prospective, nonblinded, single center. SETTING: Hospital do Servidor Público Estadual de São Paulo, in São Paulo, Brazil. PARTICIPANTS: Volunteer surgical patients. INTERVENTIONS: This prospective study evaluated adult surgical patients before and after they underwent mechanical ventilation. IcIVC and IdIVC measurements were obtained with echocardiography and PPV through arterial catheterization. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients with a mean age of 55.7 ± 10.9 years were included; 31.8% of the study participants had PPV values >13% and were shown to be responsive to fluid. A good correlation was detected between PPV and icIVC (R2 = 0.71; p < 0.001) and between PPV and idIVC (R2 = 0.79; p < 0.001). The area under the receiver operating characteristic curve was 0.98 for icIVC (95% confidence interval 0.81-0.99; p < 0.001) and 0.88 for idIVC (95% confidence interval 0.67-0.98; p < 0.001). CONCLUSIONS: PPV was found to have good correlation with the inferior vena cava diameter variation using echocardiography in surgical patients undergoing spontaneous and artificial ventilation. The cutoff values that best predicted PPV >13% were >40% for icIVC and >17.6% for idIVC.

Effects of fresh and aged vehicular exhaust emissions on breathing pattern and cellular responses--pilot single vehicle study.

The study presented here is a laboratory pilot study using diluted car exhaust from a single vehicle to assess differences in toxicological response between primary emissions and secondary products resulting from atmospheric photochemical reactions of gas phase compounds with O3, OH and other radicals. Sprague Dawley rats were exposed for 5 h to either filtered room air (sham) or one of two different atmospheres: (i) diluted car exhaust (P)+Mt. Saint Helens Ash (MSHA); (ii) P+MSHA+secondary organic aerosol (SOA, formed during simulated photochemical aging of diluted exhaust). Primary and secondary gases were removed using a nonselective diffusion denuder. Continuous respiratory data was collected during the exposure, and bronchoalveolar lavage (BAL) and complete blood counts (CBC) were performed 24 h after exposure. ANOVA models were used to assess the exposure effect and to compare those effects across different exposure types. Total average exposures were 363 ± 66 µg/m³ P+MSHA and 212 ± 95 µg/m³ P+MSHA+SOA. For both exposures, we observed decreases in breathing rate, tidal and minute volumes (TV, MV) and peak and median flows (PIF, PEF and EF50) along with increases in breathing cycle times (Ti, Te) compared to sham. These results indicate that the animals are changing their breathing pattern with these test atmospheres. Exposure to P+MSHA+SOA produced significant increases in total cells, macrophages and neutrophils in the BAL and in vivo chemiluminescence of the lung. There were no significant differences in CBC parameters. Our data suggest that simulated atmospheric photochemistry, producing SOA in the P+MSHA+SOA exposures, enhanced the toxicity of vehicular emissions.