Non-invasive accurate measurement of arterial PCO2 in a pediatric animal model

The PCO₂ in arterial blood (PaCO₂) is a good parameter for monitoring ventilation and acid–base changes in ventilated patients, but its measurement is invasive and difficult to obtain in small children. Attempts have been made to use the partial pressure of CO₂ in end-tidal gas (PetCO₂), as a noninvasive surrogate for PaCO₂. Studies have revealed that, unfortunately, the differences between PetCO₂ and PaCO₂ are too variable to be clinically useful. We hypothesized that end-inspiratory rebreathing, previously shown to equalize PetCO₂ and PaCO₂ in spontaneously breathing humans, would also be effective with positive pressure ventilation. Eight newborn Yorkshire pigs were mechanically ventilated via a partial rebreathing circuit to implement end-inspiratory rebreathing. Arterial blood was sampled and tested for PaCO₂. A variety of alveolar ventilations resulting in different combinations of end-tidal PCO₂ (30–50 mmHg) and PO₂ (35–500 mmHg) were tested for differences between PetCO₂ and PaCO₂ (Pet-aCO₂). The Pet-aCO₂ of all samples was (mean ± 1.96 SD) 0.4 ± 2.7 mmHg. Our study demonstrates that, in ventilated juvenile animals, end-inspiratory rebreathing maintains Pet-aCO₂ to what would be a clinically useful range. If verified clinically, this approach could open the way for non-invasive monitoring of arterial PCO₂ in critically ill patients.     

Bench test assessment of mainstream capnography during high frequency oscillatory ventilation

To assess the feasibility, stability and predictability of pCO₂ measurement (PetCO₂) using a main stream capnograph in a high frequency oscillatory ventilation circuit. A commercially available capnograph was mounted into a high frequency oscillatory ventilator patient circuit, adjustable CO₂ flow was introduced into an artificial lung and the output of the CO₂ sensor assessed under varying ventilator settings. Influence of oxygen content, pressures, heat and moisture were recorded. A linear relationship between CO₂ flow rate and PetCO₂ was found. Varying ventilator settings influenced the measurements, but the results for PetCO₂ remained within a range of 1.5 mmHg above or under then mean measurement value. Measurements remained stable despite humidification, heat, pressure amplitudes or mean airway pressure changes. From this bench test, we conclude it is feasible to measure PetCO₂ using a main stream capnograph during high frequency oscillatory conditions, these measurements were stable during the experiment. Changes in CO₂ production or output can be detected. The system may prove to be of clinical value, but further in vivo measurements are warranted.     

Intramucosal–arterial PCO 2 gap fails to reflect intestinal dysoxia in hypoxic hypoxia

Introduction

An elevation in intramucosal–arterial PCO ₂ gradient (ΔPCO ₂) could be determined either by tissue hypoxia or by reduced blood flow. Our hypothesis was that in hypoxic hypoxia with preserved blood flow, ΔPCO ₂ should not be altered.

Methods

In 17 anesthetized and mechanically ventilated sheep, oxygen delivery was reduced by decreasing flow (ischemic hypoxia, IH) or arterial oxygen saturation (hypoxic hypoxia, HH), or no intervention was made (sham). In the IH group (n = 6), blood flow was lowered by stepwise hemorrhage; in the HH group (n = 6), hydrochloric acid was instilled intratracheally. We measured cardiac output, superior mesenteric blood flow, gases, hemoglobin, and oxygen saturations in arterial blood, mixed venous blood, and mesenteric venous blood, and ileal intramucosal PCO ₂ by tonometry. Systemic and intestinal oxygen transport and consumption were calculated, as was ΔPCO ₂. After basal measurements, measurements were repeated at 30, 60, and 90 minutes.

Results

Both progressive bleeding and hydrochloric acid aspiration provoked critical reductions in systemic and intestinal oxygen delivery and consumption. No changes occurred in the sham group. ΔPCO ₂ increased in the IH group (12 ± 10 [mean ± SD] versus 40 ± 13 mmHg; P < 0.001), but remained unchanged in HH and in the sham group (13 ± 6 versus 10 ± 13 mmHg and 8 ± 5 versus 9 ± 6 mmHg; not significant).

Discussion

In this experimental model of hypoxic hypoxia with preserved blood flow, ΔPCO ₂ was not modified during dependence of oxygen uptake on oxygen transport. These results suggest that ΔPCO ₂ might be determined primarily by blood flow.     

Use of end-tidalPco 2 and transcutaneousPco 2 as noninvasive measurement of arterialPco 2 in extubated patients recovering from general anesthesia

This study was designed to assess the accuracy of end-tidalPco ₂ and transcutaneousPco ₂ as measurements of arterialPco ₂ in extubated, spontaneously breathing patients recovering from general anesthesia. In 30 patients, measurement of arterial transcutaneous, and end-tidalPco ₂ were taken simultaneously with body temperature approximately every 15 minutes over a 2-hour period. ArterialPco ₂ values were corrected for body temperature. Values for Paco ₂ were compared with those forPetCO₂ and Psco ₂ by linear regression analysis and by calculation of bias ± precision. Thirty-six percent of the capnogram tracings obtained did not develop a plateau phase. We found poor correlation between end-tidal and arterialPco ₂ regardless of the shape of the capnogram tracing, as well as poor correlation between transcutaneous and arterialPco ₂. Although the measurements of bias and precision of noninvasivePco ₂ monitors in this population are comparable to studies in other populations, we advise caution in relying on the routine use ofPetCO₂ or Psco ₂ for the noninvasive assessment of respiratory depression in extubated, spontaneously breathing patients recovering from general anesthesia.     

Influence of flow on mucosal-to-arterial carbon dioxide difference

Intramucosal-to-arterial carbon dioxide difference (the so-called PCO ₂ [partial carbon dioxide tension] gap) remains largely unaltered during decreased oxygen delivery, if the latter is reduced as flow is maintained. In this condition (hypoxic hypoxia or anaemic hypoxia), the PCO ₂ gap fails to mirror intestinal tissue dysoxia. Results from several experiments have demonstrated that blood flow is the main determinant of PCO ₂ gap. Gastrointestinal tonometry is clearly a useful indirect method for monitoring perfusion, but it has rather limited value in detecting anaerobic metabolism when blood flow is preserved. These considerations render it very unlikely that PCO ₂ may dramatically increase (or that intramucosal pH may decrease) in any hypoxic state with preserved flow.     

Noninvasive monitoring of carbon dioxide: A comparison of the partial pressure of transcutaneous and end-tidal carbon dioxide with the partial pressure of arterial carbon dioxide

This study compares two noninvasive techniques for monitoring the partial pressure of carbon dioxide (Pco2) in 24 anesthetized adult patients. End-tidal PCO₂ (PETCO₂) and transcutaneous Pco₂ (PtcCO₂) were simultaneously monitored and compared with arterial Pco₂ (PaCO₂) determined by intermittent analysis of arterial blood samples. PETCO₂ and PtcCO₂ values were compared with PaCO₂ values corrected to patient body temperature (PaC0_2T) and PaCO₂ values determined at a temperature of 37°C (PaCO₂). Linear regression was performed along with calculations of the correlation coefficient (r), bias, and precision of the four paired variables:PETCO₂ versus PaCO₂ and PaCO_2T (n = 211), and PtcCO₂ versus PaCO₂ and PaCO_2T (n = 233). Bias is defined as the mean difference between paired values, whereas precision is the standard deviation of the difference. The following values were found forr, bias, and ± precision, respectively.PetCO₂ versus PaCO₂: 0.67, ?7.8 mm Hg, ±6.1 mm Hg;PETCO₂ versus PaCO_2T: 0.73, ?5.8 mm Hg, ±5.9 mm Hg;PETCO₂ versus PaCO₂: 0.87, ?1.6 mm Hg, ±4.3 mm Hg; PtcCO₂ versus PaC0_2T: 0.84, +0.7 mm Hg, ±4.8 mm Hg. Although each of thesePCO ₂ variables is physiologically different, there is a significant correlation (P < 0.001) between the noninvasively monitored values and the blood gas values. Temperature correction of the arterial values (PaCO_2T) slightly improved the correlation, with respect toPETCO₂, but it had the opposite effect for PtcCO₂. In this study, the chief distinction between these two noninvasive monitors was thatPETCO₂ had a large negative bias, whereas PtcCO₂ had a small bias. We conclude from these data that PtcCO₂ may be used to estimate PaCO₂ with an accuracy similar to that ofPetCO₂ in anesthetized patients.     

Luminal concentrations of L- and D-lactate in the rectum may relate to severity of disease and outcome in septic patients

Introduction

Little is known about the condition of the large bowel in patients with sepsis. We have previously demonstrated increased concentrations of L-lactate in the rectal lumen in patients with abdominal septic shock. The present study was undertaken to assess the concentrations of L- and D-lactate in rectal lumen and plasma in septic patients including the possible relation to site of infection, severity of disease, and outcome.

Methods

An intensive care unit observational study was conducted at two university hospitals, and 23 septic patients and 11 healthy subjects were enrolled. Participants were subjected to rectal equilibrium dialysis, and concentrations of L- and D-lactate in dialysates and plasma were analysed by spectrophotometry.

Results

Luminal concentrations of L-lactate in rectum were related to the sequential organ failure assessment scores (R ² = 0.27, P = 0.01) and were higher in non-survivors compared to survivors and healthy subjects (mean [range] 5.0 [0.9 to 11.8] versus 2.2 [0.4 to 4.9] and 0.5 [0 to 1.6] mmol/l, respectively, P < 0.0001), with a positive linear trend (R ² = 0.53, P < 0.0001). Also, luminal concentrations of D-lactate were increased in non-survivors compared to survivors and healthy subjects (1.1 [0.3 to 2.5] versus 0.3 [0 to 1.2] and 0.1 [0 to 0.8] mmol/l, respectively, P = 0.01), with a positive linear trend (R ² = 0.14, P = 0.04). Luminal concentrations of L- and D-lactate were unaffected by the site of infection. Plasma concentrations of L-lactate were also increased in non-survivors compared to survivors (3.8 [1.7 to 7.0] versus 1.5 [0 to 3.6] mmol/l, P < 0.01). In contrast, plasma concentrations of D-lactate were equally raised in non-survivors (0.4 [0.1 to 0.7] mmol/l) and survivors (0.3 [0.1 to 0.6] mmol/l) compared with healthy subjects (0.03 [0 to 0.13] mmol/l).

Conclusion

In patients with severe sepsis and septic shock, luminal concentrations of L- and D-lactate in the rectum were related to severity of disease and outcome.     

Transcutaneous P<Emphasis Type="SmallCaps">tc</Emphasis>CO<Subscript>2</Subscript> measurement in combination with arterial blood gas analysis provides superior accuracy and reliability in ICU patients

Hyper or hypoventilation may have serious clinical consequences in critically ill patients and should be generally avoided, especially in neurosurgical patients. Therefore, monitoring of carbon dioxide partial pressure by intermittent arterial blood gas analysis (PaCO₂) has become standard in intensive care units (ICUs). However, several additional methods are available to determine PCO₂ including end-tidal (PetCO₂) and transcutaneous (PtcCO₂) measurements. The aim of this study was to compare the accuracy and reliability of different methods to determine PCO₂ in mechanically ventilated patients on ICU. After approval of the local ethics committee PCO₂ was determined in n = 32 ICU consecutive patients requiring mechanical ventilation: (1) arterial PaCO₂ blood gas analysis with Radiometer ABL 625 (ABL; gold standard), (2) arterial PaCO₂ analysis with Immediate Response Mobile Analyzer (IRMA), (3) end-tidal PetCO₂ by a Propaq 106 EL monitor and (4) transcutaneous PtcCO₂ determination by a Tina TCM4. Bland–Altman method was used for statistical analysis; p < 0.05 was considered statistically significant. Statistical analysis revealed good correlation between PaCO₂ by IRMA and ABL (R² = 0.766; p < 0.01) as well as between PtcCO₂ and ABL (R² = 0.619; p < 0.01), whereas correlation between PetCO₂ and ABL was weaker (R² = 0.405; p < 0.01). Bland–Altman analysis revealed a bias and precision of 2.0 ± 3.7 mmHg for the IRMA, 2.2 ± 5.7 mmHg for transcutaneous, and ?5.5 ± 5.6 mmHg for end-tidal measurement. Arterial CO₂ partial pressure by IRMA (PaCO₂) and PtcCO₂ provided greater accuracy compared to the reference measurement (ABL) than the end-tidal CO₂ measurements in critically ill in mechanically ventilated patients patients.     

Effect of l-NAME, an inhibitor of nitric oxide synthesis, on plasma levels of IL-6, IL-8, TNFα and nitrite/nitrate in human septic shock

Objectives: We tested the effects of N^G-nitro-L-arginine methyl ester (l-NAME), an inhibitor of nitric oxide (NO) synthesis, on plasma levels of interleukin (IL) IL-6, IL-8, tumor necrosis factor-alpha (TNFα) and nitrite/nitrate (NO ₂ ^? /NO ₃ ^? ) in patients with severe septic shock. Design: Prospective clinical study. Setting: Surgical intensive care unit at a university hospital. Patients: 11 consecutive patients with severe septic shock. Interventions: Standard hemodynamic measurements were made and blood samples taken at intervals before, during, and after a 12-h infusion of l-NAME 1 mg · kg^?1 ·h^?1 for determination of plasma IL-6, IL-8, TNFα and NO ₂ ^? /NO ₃ ^? concentration. Measurements and results: Patients with sepsis had increased plasma levels of IL-6, IL-8, TNFα, and NO ₂ ^? /NO ₃ ^? (p<0.05). Plasma levels of IL-6, IL-8, and NO ₂ ^? /NO ₃ ^? were negatively correlated with systemic vascular resistance (r=?0.62, r=?0.65, and r=?0.78, respectively, all p<0.05). Continuous infusion of l-NAME increased mean arterial pressure and systemic vascular resistance, with a concomitant reduction in cardiac output (all p<0.01). No significant changes were seen in levels of plasma IL-6, IL-8, and NO ₂ ^? /NO ₃ ^? during the 24-h observation period. Plasma levels of TNFα were significantly reduced during l-NAME infusion compared to baseline (p<0.05). Conclusions: NO plays a role in the cardiovascular derangements of human septic shock. Inhibition of NO synthesis with l-NAME does not promote excessive cytokine release in patients with severe sepsis.     

A randomized trial of intravenous glutamine supplementation in trauma ICU patients

Purpose

To evaluate the effect of the intravenous (i.v.) l-alanyl-l-glutamine dipeptide supplementation during 5 days on clinical outcome in trauma patients admitted to the intensive care unit (ICU).

Methods

This was a prospective, randomized, double-blind, multicenter trial. Glutamine was not given as a component of nutrition but as an extra infusion. The primary outcome variable was the number of new infections within the first 14 days.

Results

We included 142 patients. There were no differences between groups in baseline characteristics. Up to 62 % of the patients in the placebo group and 63 % in the treatment group presented confirmed infections (p = 0.86). ICU length of stay was 14 days in both groups (p = 0.54). Hospital length of stay was 27 days in the placebo group and 29 in the treatment group (p = 0.88). ICU mortality was 4.2 % in both groups (p = 1). Sixty percent of the patients presented low glutamine levels before randomization. At the end of the treatment (6th day), 48 % of the patients maintained low glutamine levels (39 % of treated patients vs. 57 % in the placebo group). Patients with low glutamine levels at day 6 had more number of infections (58.8 vs. 80.9 %; p = 0.032) and longer ICU (9 vs. 20 days; p < 0.01) and hospital length of stay (24 vs. 41 days; p = 0.01).

Conclusions

There was no benefit with i.v. l-alanyl-l-glutamine dipeptide supplementation (0.5 g/kg body weight/day of the dipeptide) during 5 days in trauma patients admitted to the ICU. The i.v. glutamine supplementation was not enough to normalize the plasma glutamine levels in all patients. Low plasma glutamine levels at day 6 were associated with a worse outcome.     

25-Hydroxyvitamin D insufficiency is associated with impaired renal endothelial function and both are improved with rosuvastatin treatment

Background

Vitamin D deficiency is nowadays considered as a potential cardiovascular and renal risk factor. We tested the hypotheses that vitamin D deficiency impairs the endothelial function of renal vasculature and whether vitamin D levels and endothelial function can be improved by the treatment with statins.

Methods

In a double-blind, randomized study of 31 hypercholesterolemic patients with vitamin D insufficiency (<30 ng/ml) were randomly assigned to rosuvastatin (10 mg/d) and placebo for 6 weeks. Basal nitric oxide (NO) activity of the renal vasculature was assessed both before and after the blockade of NO synthases with systemic infusion of N(G)-monomethyl-l-arginine (l-NMMA). In parallel, 25(OH)D was measured.

Results

Multiple regression analysis revealed that at baseline 25(OH)D is an independent determinant of basal NO activity as assessed by the decrease in RPF, in response to l-NMMA (β = ?0.446, r = 0.015). Compared to placebo treatment, rosuvastatin increased 25(OH)D levels (21.6 ± 4.0 vs. 24.1 ± 8.1 ng/ml, p = 0.039). Basal NO activity was significantly more increased after 6-week therapy with rosuvastatin than with placebo (?94.8 ± 70 vs. ?68.2 ± 32 ml/min, p = 0.044), indicating increased basal NOS activity after 6 weeks of rosuvastatin treatment. Basal NO activity in the placebo phase was correlated inversely with 25(OH)D (r = ?0.385; p = 0.027).

Conclusions

Thus, vitamin D insufficiency is associated with impaired endothelial function in the renal vasculature and both were beneficially influenced by the treatment with rosuvastatin.     

Comparison of volumetric capnography and mixed expired gas methods to calculate physiological dead space in mechanically ventilated ICU patients

Introduction

Physiological dead space should be a routine measurement in ventilated patients but measuring dead space using the Douglas bag (DB) method is cumbersome and requires corrections for compressed ventilator gas. These factors make this method impractical in the critical care setting. Volumetric capnography (VCAP) offers a relatively simple solution to calculating dead space. Few studies have been conducted to directly compare dead space measured by VCAP and the DB method in critically unwell adults.

Method

Prospective observational study of 48 mechanically ventilated adults ICU patients. Dead space was calculated simultaneously using VCAP (CO₂SMO) and the Bohr–Enghoff equation. In total, 168 paired readings were taken. Single-breath CO₂ waveform areas under the curve were computed automatically by software to calculate physiological dead space. The calculated value of $ P_{{\bar{E}_{{{\text{CO}}_{2} }} }} $ was also recorded from the CO₂SMO device. Exhaust ventilator gas was collected in a 10-l mixing chamber. $ P_{{\bar{E}_{{{\text{CO}}_{2} }} }} $ was measured in the chamber following correction for compressed gas.

Results

The study demonstrated good agreement between physiological V _D/V _T calculated by VCAP and corrected (mean bias 0.03), and uncorrected (mean bias 0.02) Bohr–Enghoff method. There was good correlation between the two methods of measurement (VCAP vs corrected r ²?=?0.90 P?<?0.001, VCAP vs uncorrected r ²?=?0.90, P?<?0.001). There was good correlation between $ P_{{\bar{E}_{{{\text{CO}}_{2} }} }} $ calculated by the CO₂SMO and in the exhaust collected gas (mean bias 0.08).

Conclusions

VCAP shows good agreement with Douglas Bag method in measuring physiological V _D/V _T over a wide range of dead space fractions.     

Metabolism of Radiolabeled Methionine in Hepatocellular Carcinoma

Purpose

Radiolabeled methionine (Met) promises to be useful in the positron emission tomography (PET) imaging of hepatocellular carcinoma (HCC). However, its metabolic routes in HCC have not yet been fully understood. In this study, the metabolic pathway(s) of radiolabeled Met in HCC were investigated.

Procedures

To simulate the rapid blood clearance of radiolabeled Met, pulse–chase experiments were conducted. l-[methyl-³H]-Met or l-[1-¹⁴C]-Met was pulsed over control or cycloheximide-treated WCH17 cells and rat hepatocytes for 5 min and chased with cold media. The water-soluble, lipid-soluble, DNA, RNA, and protein phases were subsequently extracted and measured from the acid-precipitable and acid-soluble fractions of whole cells. The radioactive metabolites Met, S-adenosylmethionine (SAM), S-adenosylhomocysteine, Met sulfoxide, and Met sulfone were further separated by radio thin layer chromatography.

Results

(1) The uptake of l-[methyl-³H]-Met in both cell types was higher than that of l-[1-¹⁴C]-Met. In rat hepatocytes, the uptake of l-[methyl-³H]-Met was significantly higher than that of l-[1-¹⁴C]-Met, which may contribute to its physiologic accumulation in surrounding hepatic tissues seen in PET imaging of HCC using l-[methyl-¹¹C]-Met. Compared to rat hepatocytes, WCH17 cells had significantly higher uptake of both radiotracers. (2) For l-[methyl-³H]-Met, the major intracellular uptake was found mostly in the protein phase and, to a lesser degree, in the phosphatidylethanolamine (PE) methylation pathway, which is fairly stabilized within the 55-min chase period (the main metabolites were SAM, Met, Met sulfoxide, and Met sulfone). In contrast, the uptake of Met in rat hepatocytes mainly points to phosphatidylcholine (PC) synthesis through the PE methylation pathway (the main metabolite was PC). (3) Both cell types incorporated l-[1-¹⁴C]-Met predominantly into protein synthesis. (4) Finally, when the protein synthesis pathway was inhibited, the incorporation of SAM derived from l-[methyl-³H]-Met to lipid class (PC was the main metabolite) occurred at a reduced rate in WCH17 cells, suggesting that the route may be impaired in HCC.

Conclusions

This study demonstrated that different metabolic pathways of radiolabeled Met exist between HCC and surrounding hepatic tissue and contribute to the patterns of increased uptake of radiolabeled Met in HCC.     

Typical patterns of expiratory flow and carbon dioxide in mechanically ventilated patients with spontaneous breathing

Incomplete expiration of tidal volume can lead to dynamic hyperinflation and auto-PEEP. Methods are available for assessing these, but are not appropriate for patients with respiratory muscle activity, as occurs in pressure support. Information may exist in expiratory flow and carbon dioxide measurements, which, when taken together, may help characterize dynamic hyperinflation. This paper postulates such patterns and investigates whether these can be seen systematically in data. Two variables are proposed summarizing the number of incomplete expirations quantified as a lack of return to zero flow in expiration (IncExp), and the end tidal CO₂ variability (varetCO₂), over 20 breaths. Using these variables, three patterns of ventilation are postulated: (a) few incomplete expirations (IncExp < 2) and small varetCO₂; (b) a variable number of incomplete expirations (2 ≤ IncExp ≤ 18) and large varetCO₂; and (c) a large number of incomplete expirations (IncExp > 18) and small varetCO₂. IncExp and varetCO₂ were calculated from data describing respiratory flow and CO₂ signals in 11 patients mechanically ventilated at 5 levels of pressure support. Data analysis showed that the three patterns presented systematically in the data, with periods of IncExp < 2 or IncExp > 18 having significantly lower variability in end-tidal CO₂ than periods with 2 ≤ IncExp ≤ 18 (p < 0.05). It was also shown that sudden change in IncExp from either IncExp < 2 or IncExp > 18 to 2 ≤ IncExp ≤ 18 results in significant, rapid, change in the variability of end-tidal CO₂ p < 0.05. This study illustrates that systematic patterns of expiratory flow and end-tidal CO₂ are present in patients in supported mechanical ventilation, and that changes between these patterns can be identified. Further studies are required to see if these patterns characterize dynamic hyperinflation. If so, then their combination may provide a useful addition to understanding the patient at the bedside.     

Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro

Objective: To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro.¶Design and setting: Prospective study in a university pediatric intensive care ward and research laboratory.¶Patients and materials: Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro.¶Interventions: NO inhalation and withdrawal in patients; exposure to NO donor sodium nitroprusside (SNP) and gaseous NO in vitro.¶Measurements and results: In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 ± 0.24 cmH₂O/torr (mean ± SEM) to 4.90 ± 0.26 cmH₂O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 ± 0.23 cmH₂O/torr) 30 min after weaning, a significant drop after 4 h (3.72 ± 0.17 cmH₂O/torr; p < 0.001), values restored after 12 h.¶In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 ± 4.0 μm/min) than in control cells (37.6 ± 7.0 μm/min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 ± 10.0 μm/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot).¶Conclusion: In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.     

Discrepancy of in-vitro data and clinical efficacy of micafungin against Candida tropicalis endophthalmitis

We report findings for a 74-year-old woman with Candida tropicalis endophthalmitis for whom an increase in β-d-glucan level and worsening of endophthalmitis were observed after intravenous injection of micafungin, an echinocandin antifungal agent. Endogenous endophthalmitis caused by C. tropicalis developed in both eyes. On the basis of her surgical history, laboratory data, and lesions, tentative diagnosis of fungal endophthalmitis was made. She was then treated with fluconazole and itraconazole, but the β-d-glucan level did not decrease, and there was no improvement of the endophthalmitis. The fluconazole was discontinued and replaced by micafungin. Unexpectedly, the level of β-d-glucan increased and endophthalmitis did not improve. The micafungin was immediately stopped and replaced by intravenous fluconazole with amphotericin B syrup, but the itraconazole was continued. Marked resolution of the vitreous inflammation was observed in both eyes, and the serum β-d-glucan level was reduced. Because active macular infiltrates were observed in the right eye, vitrectomy was performed. The micafungin minimum inhibitory concentration against the C. tropicalis strain isolated from our patient was 0.03 μg/ml. This paradoxical effect of micafungin should be remembered, and β-d-glucan level should be frequently monitored after intravenous injection of micafungin.     

Partial pressure of end-tidal carbon dioxide successful predicts cardiopulmonary resuscitation in the field: a prospective observational study

Introduction

Prognosis in patients suffering out-of-hospital cardiac arrest is poor. Higher survival rates have been observed only in patients with ventricular fibrillation who were fortunate enough to have basic and advanced life support initiated soon after cardiac arrest. An ability to predict cardiac arrest outcomes would be useful for resuscitation. Changes in expired end-tidal carbon dioxide levels during cardiopulmonary resuscitation (CPR) may be a useful, noninvasive predictor of successful resuscitation and survival from cardiac arrest, and could help in determining when to cease CPR efforts.

Methods

This is a prospective, observational study of 737 cases of out-of-hospital cardiac arrest. The patients were intubated and measurements of end-tidal carbon dioxide taken. Data according to the Utstein criteria, demographic information, medical data, and partial pressure of end-tidal carbon dioxide (Pet CO ₂) values were collected for each patient in cardiac arrest by the emergency physician. We hypothesized that an end-tidal carbon dioxide level of 1.9 kPa (14.3 mmHg) or more after 20 minutes of standard advanced cardiac life support would predict restoration of spontaneous circulation (ROSC).

Results

Pet CO ₂ after 20 minutes of advanced life support averaged 0.92 ± 0.29 kPa (6.9 ± 2.2 mmHg) in patients who did not have ROSC and 4.36 ± 1.11 kPa (32.8 ± 9.1 mmHg) in those who did (P < 0.001). End-tidal carbon dioxide values of 1.9 kPa (14.3 mmHg) or less discriminated between the 402 patients with ROSC and 335 patients without. When a 20-minute end-tidal carbon dioxide value of 1.9 kPa (14.3 mmHg) or less was used as a screening test to predict ROSC, the sensitivity, specificity, positive predictive value, and negative predictive value were all 100%.

Conclusions

End-tidal carbon dioxide levels of more than 1.9 kPa (14.3 mmHg) after 20 minutes may be used to predict ROSC with accuracy. End-tidal carbon dioxide levels should be monitored during CPR and considered a useful prognostic value for determining the outcome of resuscitative efforts and when to cease CPR in the field.     

Nutritional supplements and plasma antioxidants in childhood asthma

Objective

This study investigated the relationship of plasma antioxidants to airway inflammation and systemic oxidative stress in children suffering from atopic asthma with consideration of the intake of nutritional supplements.

Subjects and research methods

A total of 35 asthmatic children (AG) and 21 healthy controls (CG) participated in this study. Plasma levels of vitamins A and E, β-carotene, coenzyme Q10 and malondialdehyde (MDA) were analyzed with high-performance liquid chromatography (HPLC); the total antioxidant capacity (TAC) was measured photometrically, and selenium was determined by atomic absorption spectroscopy (AAS). The volume of fractionated exhaled nitric oxide (FeNO) was measured with the NIOX nitric oxide monitoring system.

Results

The plasma antioxidants vitamins A and E, selenium, and coenzyme Q10 but not β-carotene were significantly (p < 0.05) lower in asthmatics than in controls. Further, asthmatic children had significantly reduced plasma concentrations of TAC (p < 0.01), significantly enhanced levels of MDA (p < 0.001), and exhaled a significantly (p < 0.001) higher mean volume of FeNO than healthy children. Regular intake of supplements had a significant positive influence on plasma vitamin E (p < 0.01), selenium (p < 0.01), TAC (p < 0.05), MDA (p < 0.01), and FeNO (p < 0.01) in asthmatics but not in controls. Additionally, significant negative associations of vitamin E and MDA (AG: p < 0.01; CG: p < 0.05), and vitamin E and FeNO (AG: p < 0.05; CG: p > 0.05) were identified.

Conclusion

These results indicate that nutritional supplements beneficially modulate plasma antioxidants and thus might have a positive influence on systemic redox balance and subsequently, pulmonary inflammation in asthmatic children.     

Detection of the Prodrug-Activating Enzyme Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance

Purpose

The purpose of this study is to evaluate if the differential exchange rates with bulk water between amine and amide protons can be exploited using chemical exchange saturation transfer magnetic resonance (CEST-MR) to monitor the release of glutamate induced by carboxypeptidase G2 (CPG2), an enzyme utilized in cancer gene therapy.

Procedures

Z spectra of solutions of the CPG2 substrate, 3,5-difluorobenzoyl-l-glutamate (amide), and glutamate (amine) were acquired at 11.7 T, 37 °C, across different pH (5–8). The ability of CEST-MR to monitor CPG2-mediated release of glutamate was assessed in extracts of CPG2-expressing cancer cells and purified solution of CPG2.

Results

The addition of CPG2 to a solution containing 3,5-difluorobenzoyl-l-glutamate led to a marked and progressively increasing CEST effect (+3 ppm), concomitant with the time-dependent release of glutamate induced by CPG2.

Conclusion

CEST-MR allows the detection of CPG2 activity in vitro and supports the translation of CEST-MRI to assess CPG2-based gene therapy in vivo.