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W Karzai

Publications and source records attributed to W Karzai.

At least 19 recordsLinked to original sources
PubMed2001

Oxygenation during one-lung ventilation: the effects of inhaled nitric oxide and increasing levels of inspired fraction of oxygen.

UNLABELLED: We studied whether inhaled nitric oxide (NO) would improve arterial oxygen tension (PaO(2)) and reduce the occurrence of oxygen saturation of hemoglobin (O(2)Hb) < 90% during one-lung ventilation (OLV). One-hundred-fifty-two patients were ventilated either with or without NO (20 ppm) with an inspired fraction of oxygen (FIO(2)) of either 0.3, 0.5, or 1.0 during OLV. Anesthesia was induced and maintained with propofol, remifentanil, and rocuronium IV, and lung separation was achieved with a double-lumen tube. During OLV, we set positive end-expiratory pressure at 5 cm H(2)O, peak pressure at 30 cm H(2)O, and end-tidal CO(2) at 30 mm Hg. The nonventilated lung was opened to room air and collapsed. During OLV, three consecutive measurements were performed every 10 min. The operated lung was temporarily ventilated if pulse oximetric saturation (SpO(2)) decreased to < 91%. SpO(2) <9 1% occurred in 2 of the 152 patients. SpO(2) overestimated O(2)Hb by 2.9% +/- 0.1%. NO failed to improve oxygenation or alter occurrence of O(2)Hb < 90% during OLV across all time points and all levels of FIO(2). Increasing FIO(2) increased oxygenation and decreased occurrence of O(2)Hb < 90% (P: < 0.001). At FIO(2) = 1, PaO(2) was higher (P < 0.01) and O(2)Hb < 90% rate tended to be lower (P = 0.1) during right versus left lung ventilation. PaO(2) was higher in patients undergoing pneumonectomy and lobectomy than in those undergoing metastasectomy or video-assisted operations (P < 0.05). IMPLICATIONS: Inhaled nitric oxide failed to improve oxygenation during one-lung ventilation. Oxygenation during one-lung ventilation was improved with increasing levels of FIO(2) during ventilation of the right versus the left lung and with increasing pathology of the nonventilated lung.

Adult↗
PubMed2001

The effects of increasing concentrations of isoflurane and desflurane on pulmonary perfusion and systemic oxygenation during one-lung ventilation in pigs.

UNLABELLED: During one-lung ventilation (OLV), hypoxic pulmonary vasoconstriction (HPV) reduces venous admixture and attenuates the decrease in arterial oxygen tension by diverting blood from the nonventilated lung to the ventilated lung. In vitro, desflurane and isoflurane depress HPV in a dose-dependent manner. Accordingly, we studied the effects of increasing concentrations of desflurane and isoflurane on pulmonary perfusion, shunt fraction, and PaO(2) during OLV in vivo. Fourteen pigs (30-42 kg) were anesthetized, tracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a left-sided double-lumen tube (DLT) was placed via tracheotomy. After DLT placement, FIO(2) was adjusted at 0.8 and anesthesia was continued in random order with 3 concentrations (0.5, 1.0, and 1.5 minimal alveolar concentrations) of either desflurane or isoflurane. Differential lung perfusion was measured with colored microspheres. All measurements were made after stabilization at each concentration. Whereas mixed venous PO(2), mean arterial pressure, cardiac output, nonventilated lung perfusion, and shunt fraction decreased in a dose-dependent manner, PaO(2) remained unchanged with increasing concentrations of desflurane and isoflurane during OLV. In conclusion, increasing concentration of desflurane and isoflurane did not impair oxygenation during OLV in pigs. IMPLICATIONS: In an animal model of one-lung ventilation, increasing concentrations of desflurane and isoflurane dose-dependently decreased shunt fraction and perfusion of the nonventilated lung and did not impair oxygenation. The decreases in shunt fraction are likely the result of anesthetic-induced marked decreases in cardiac output and mixed venous saturation.

Anesthetics, Inhalation↗
PubMed2001

Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned.

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.

Antibodies, Monoclonal↗
PubMed2001

Acute G-CSF therapy is not protective during lethal E. coli sepsis.

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 x 10(3)/mm(3) at 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.

Animals↗
PubMed2000

The effects of inhibiting leukocyte migration with fucoidin in a rat peritonitis model.

OBJECTIVES: To study the effects of fucoidin on leukocyte rolling and emigration and bacterial colonization in a peritonitis sepsis model in rats. DESIGN AND INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Animals↗
PubMed1999

The effects of increasing concentrations of desflurane on systemic oxygenation during one-lung ventilation in pigs.

UNLABELLED: 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: N2O/O2 50%/50%, desflurane 3%, propofol 50 microg x kg(-1) min(-1), and vecuronium 0.2 mg x kg(-1) x h(-1) IV), orotracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a leftsided, 28F, double-lumen tube was placed via tracheotomy. After double-lumen tube placement, N2O and desflurane were discontinued, propofol was increased to 200 microg x kg(-1) x 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.

Anesthetics, Inhalation↗
PubMed1999

Sensitivity and specificity of various markers of inflammation for the prediction of tumor necrosis factor-alpha and interleukin-6 in patients with sepsis.

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.

Adolescent↗
PubMed1999

G-CSF during Escherichia coli versus Staphylococcus aureus pneumonia in rats has fundamentally different and opposite effects.

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.

Animals↗
PubMed1999

Editorial comment.

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Journal Article↗
PubMed1998

[Procalcitonin. A new diagnostic parameter for severe infections and sepsis].

Procalcitonin (PCT), a glycoprotein consisting of 116 amino acids, has been proposed as a new marker of severe infection. The site of production under this condition remains unknown. The serum PCT concentration is determined by an immunoluminometric assay of 40 microliters serum or plasma requiring approximately two hours. Elevations of PCT are for instance associated with levels of lipopolysaccharide and the cytokines TNF-alpha and IL-6. Bacterial, parasitic or fungal infections developing septic complications in contrast to local infections, often show values exceeding 2 ng/ml. The specificity of the parameter in this context increases with its concentrations. Therapeutic actions that confine the infection locally are reflected by a decrease of the PCT value. PCT may be elevated within the first days after extended surgery or polytrauma, in some malignancies, heat-stroke and during treatment of some hematologic diseases without an existing sepsis or severe infection. Previous studies indicate certain benefits of PCT compared to traditional markers of inflammation or sepsis, where the ability to indicate a generalized infection is the primary advantage.

Biomarkers↗
PubMed1998

Effect of plasma and LPS on respiratory burst of neutrophils in septic patients.

OBJECTIVE: To compare the respiratory burst of neutrophils in sepsis and control patients using lipopolysaccharide (LPS), autologous plasma, and a combination of the two. DESIGN: Prospective, consecutive case study. SETTING: A 16-bed intensive care unit (ICU) in a university teaching hospital. INTERVENTIONS: None. PATIENTS: Plasma was obtained from 23 healthy patients scheduled for minor surgery immediately prior to induction of anesthesia (controls) and from 23 ICU patients within 24 h of diagnosis of sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: Respiratory burst was determined by lucigenin chemiluminescence expressed as mean +/- SEM of peak values of relative light units per neutrophil. There were no significant differences between neutrophils of septic patients and controls for the stimuli saline, phorbol myristate acetate, formyl-methionyl-leucyl-phenylalanine, and LPS alone. Septic patients showed a lower respiratory burst than controls (p < 0.05) under the following stimuli: plasma alone (5911 +/- 803 vs 15,397 +/- 3038) and LPS and plasma combined (13,857 +/- 1537 vs 23,026 +/- 2640). However, when stimulated with plasma after priming with LPS, septic patients elicited a higher value than control subjects (11,373 +/- 1758 vs 5987 +/- 1234, p < 0.05). CONCLUSIONS: (1) Some components of the plasma of septic patients may have a profound effect on neutrophil response; (2) plasma as a respiratory burst stimulus differentiates between sepsis and non-sepsis samples better than other common stimuli; (3) precautions must be taken when using plasma together with LPS because of the different response depending on whether LPS-priming precedes the plasma stimulus or both are introduced simultaneously and whether septic or nonseptic plasma is used.

Adult↗