Similar long-term efficacy of dual therapy containing raltegravir and a boosted protease inhibitor versus standard triple therapies in pretreated HIV-1-infected patients in a retrospective, real-life cohort of 14 years.

OBJECTIVES: Raltegravir is used in many antiretroviral combinations, but its use in treatment-experienced patients without knowledge of baseline resistance is discussed controversially as a number of comparative studies have shown a higher rate of virological failure. However, it has been used frequently for the management of treatment failure, as it was the first integrase inhibitor to become available, and thus offered new options for patients with multiple resistance. The strategic use of raltegravir in this setting is examined in this study. METHODS: In order to examine the efficacy of raltegravir in second and later lines of antiretroviral combinations, data for 740 patients from three clinical cohorts were analysed with a focus on the combinations that were used. These were stratified into the combination of two nonnucleoside reverse transcriptase inhibitors and raltegravir (2NRTIs + RAL), the combination of a boosted protease inhibitor and raltegravir (bPI + RAL), and other raltegravir-containing combinations. RESULTS: The overall rate of virological suppression to < 50 HIV-1 RNA copies/mL was 69.5%. Although the baseline rate of virological suppression was higher for 2NRTIs + RAL than for the other strata, the outcomes were similar for all three groups at weeks 24, 48, 72 and 96. CONCLUSIONS: These data indicate that, in a real-life setting, raltegravir can be used with a high virological success rate in treatment-experienced patients, and that the different combinations analysed (2NRTIs + RAL, bPI + RAL and others) show comparable rates of virological suppression.

Why hyperoxia matters during acute anemia.

BACKGROUND: Given the low physical solubility of oxygen (O2) in plasma, little value is attached to hyperoxic ventilation (FiO2 1.0) as a modality for improving O2 transport and tissue oxygen supply when hypoxemia (i.e., O2 partial pressure (paO2) <60 mmHg) is absent. Because recent experimental and clinical data conflict with this notion, we used mathematical modeling to reevaluate efficacy of hyperoxic ventilation in improving tissue oxygenation in the absence of hypoxemia by specifying its theoretical efficacy in terms of hemoglobin (Hb) equivalents. METHODS: A mathematical approach was used based on the assumption that efficacy of hyperoxic ventilation depends on the additional amount of O2 dissolved in plasma and is influenced by the high biological availability of the additional O2 provided at high paO2. This approach was used to calculate the amount of additional Hb necessary to increase the amount of utilizable O2 to the same extent as hyperoxic ventilation (the so-called "Hb equivalent"). RESULTS: Although former estimations strongly underestimated efficacy of hyperoxic ventilation (Hb equivalent, 1-2 g/dL), our more exact mathematical approach revealed a theoretical Hb equivalent of hyperoxic ventilation in the range of 3-7 g/dL, which depended on basic physiological conditions like pulmonary function, Hb concentration, and peripheral shunt perfusion. CONCLUSION: Hyperoxic ventilation establishes a highly available source of O2 that can be utilized effectively for tissue oxygenation. Although further experimental studies are required to quantify this theoretically calculated amount of utilizable O2, these results suggest that the tissue oxygenation efficacy of hyperoxic ventilation, even in absence of hypoxemia, is grossly underestimated in daily clinical practice.

Effects of alterations of inspiratory oxygen fractions on heart rate variability.

BACKGROUND: Changes in heart rate variability (HRV) during anaesthesia depend on multiple influences such as hypnosis, analgesia, surgical stress, and interacting drugs. Several recent studies have aimed to establish HRV-based monitoring tools to measure perioperative stress or anaesthetic depth. Although hyperoxic ventilation (HV) is known to alter autonomic cardiovascular regulation, there have been no studies investigating its influence on time- and frequency-domain analysis during general anaesthesia. Therefore, we have examined the effects of HV on cardiovascular neuroregulation of anaesthetized patients and conscious volunteers by analysis of relevant HRV parameters. METHODS: Fourteen healthy volunteers and 14 anaesthetized, ventilated ASA I patients sequentially breathed room air ( 0.21), pure oxygen ( 1.0), and then room air. During each episode, standardized HRV parameters were calculated from 5 min ECG recordings. RESULTS: HV significantly reduced HR and increased the standard deviation of RR interval values, the root mean square of successive RR interval differences, and the high-frequency (HF) power of the spectral components, whereas the low-frequency (LF) power and the LF/HF ratio of HRV were reduced in both groups. All changes were reversible after was reduced to normoxia. CONCLUSIONS: In both healthy volunteers and anaesthetized patients, HV resulted in comparable and reversible changes of established HRV parameters. These changes might be relevant enough to bias HRV-based analgesia and anaesthesia monitoring and could result in a clinically relevant misinterpretation of HRV parameters as indicators of anaesthetic depth during HV.

Effects of hyperoxic ventilation on 6-h survival at the critical haemoglobin concentration aggravated by experimentally induced tachycardia in anaesthetized pigs.

AIM: Administration of 100% oxygen [hyperoxic ventilation (HV)] has been proven to ameliorate oxygen transport, tissue oxygenation and survival in different models of extreme normovolemic and hypovolemic anaemia. However, up to date, it is unknown whether HV is also able to improve outcome of extreme anaemia if myocardial oxygen consumption is contemporaneously increased by tachycardia. Therefore, we investigated the influence of HV on the 6-h survival rate during extreme anaemia and aggravated by experimentally induced tachycardia in a prospective, randomized study in a pig model of critical anaemia. METHODS: After government approval, 14 anesthetized pigs mechanically ventilated on room air were haemodiluted by replacing a certain amount of whole blood with hydroxethyl starch 6% (200.000/0.5) until their individual critical haemoglobin concentration (Hb(crit)) was achieved. At Hb(crit), tachycardia (180 bpm) was induced in all animals by atrial pacing. Thereafter, animals were observed for the next 6 h either at room air (FiO(2) 0.21; group NOX) or during HV (FiO(2) 1.0; group HOX) without further intervention. As primary outcome parameter of this study, the 6-h survival rate was selected. RESULTS: Hyperoxic ventilation increased the 6-h survival rate from 14 to 100%. In contrast to the NOX group, macrohaemodynamics and oxygen transport improved in the HOX group during the observation period without apparent adverse effects of HV. CONCLUSIONS: Hyperoxic ventilation can be considered a safe and effective measure for the optimization of oxygen supply during extreme anaemia and despite concomitant tachycardia within 6 h. Whether HV can also be recommended beyond this period warrants further studies.

Changes in heart rate variability across different degrees of acute dilutional anemia.

BACKGROUND: We investigated changes in heart rate variability (HRV) across different degrees of acute dilutional anemia (hemoglobin [Hb]=9, 7, 5, 4, and 3 g/dL) in a pig model. METHODS: Twelve anesthetized mechanically ventilated pigs of either gender (mean body weight 27.5±5.5 kg) were hemodiluted by exchange of blood for hydroxyethyl starch (6%; 200000/0.5) from baseline values to each animal's individual critical hemoglobin concentration (Hbcrit 3.3 [2.3/3.6] g/dL). Differences in time- and frequency-domain calculations of HRV were analyzed throughout the hemodilution procedure by using short-term electrocardiogram recordings (analysis of variance+Dunn's post-hoc test). RESULTS: During the hemodilution procedure, the standard deviation of normal R-R intervals and the coefficient of variation changed at Hb 5.3 (4.2/5.7) g/dL. Thereafter, the high-frequency power (HF), total power of the variance, and root mean square of successive N-N interval differences changed at Hb 3.9 (3.1/4.3) g/dL. The low-frequency power (LF) and the LF/HF ratio remained unaffected by hemodilution to Hbcrit. CONCLUSION: Acute dilutional anemia resulted in significant changes in different time- and frequency-domain variables in HRV analysis. These changes occurred considerably earlier than did commonly recognized transfusion triggers or signs of general tissue hypoxia. Further investigation is warranted to elucidate whether these changes can be considered as indicators of imminent tissue hypoxia.