Investigation of the effects of naratriptan,rizatriptan, and sumatriptan on jugular venous oxygen saturation in anesthetized pigs: implications for their mechanism of acute antimigraine action

The effects of naratriptan, rizatriptan, and sumatriptan on arteriovenous oxygen saturation difference and carotid hemodynamics were compared in the anesthetized pig. Oxygen and carbon dioxide partial pressures in systemic arterial and jugular venous blood as well as hemoglobin oxygen saturation were determined by conventional blood gas analysis. Vehicle (n = 19) or naratriptan, rizatriptan, or sumatriptan (0.63, 2.5, 10, 40, 160, 630, and 2,500 microg/kg i.v.; n = 7/group) were infused cumulatively. In naratriptan-, rizatriptan-, and sumatriptan-treated animals, jugular venous oxygen saturation decreased dose dependently (geometric mean ED50 values of 3.1, 17.9, and 16.0 microg/kg, respectively) concomitantly with increases in carotid vascular resistance. Rizatriptan significantly and dose dependently, from 160 microg/kg, increased PvCO2 (P < 0.05 versus vehicle). Naratriptan and sumatriptan also tended to increase PvCO2 albeit nonstatistically significantly. All three triptans consistently evoked quantitatively similar carotid vasoconstriction, whereas decreases in jugular venous oxygen saturation (VOS) and increases in PvCO2 had different magnitudes and occurred only in around one-half of the animals studied. Maximal variations in PvCO2 were found to correlate highly with those in PvO2 (P = 0.002), but maximal variations in carotid resistance failed to correlate with those in PvCO2 (P = 0.76) or PvO2 (P = 0.28). The results demonstrate that the triptans investigated robustly produced carotid vasoconstriction, but elicited less consistent decreases in VOS and increases in jugular PvCO2, possibly suggestive of distinct mechanisms. Collectively, the data suggest that triptan-induced increases in arteriovenous oxygen saturation difference and carbon dioxide partial pressure in venous blood draining the head are class effects.     

颈内静脉球血氧饱和度监测的临床应用

颈内静脉球血氧饱和度(jugular venous bulb oxygen saturation,SjvO2)监测可及早发现脑氧供需的变化,尽早治疗以减轻脑组织的缺血缺氧性损伤。在神经外科手术、体外循环(cardiopulmonary bypass,CPB)和特殊体位手术中应用广泛,与脑组织氧分压(partial oxygen pressure of brain tissue,PbtO2)和近红外光谱对比有其优势,还可用于围手术期生理探索、指导过度通气、综合脑保护和多模式监测等诊治手段。     

重型颅脑伤患者颈静脉血氧饱和度的监测及其临床意义

目的：探讨重型颅脑创伤后颈静脉血氧饱和度（ＳｊＯ２）的变化以及临床意义。方法：重型颅脑创伤患者３３例，格拉斯哥昏迷评分（ＧＣＳ）平均５．４６分，入院后经皮穿刺颈内静脉留置导管，监测ＳｊＯ２，同时监测颅内压（ＩＣＰ）、动脉氧饱和度（ＳａＯ２）、脉搏氧饱和度（ＳｐＯ２）以及颈静脉、动脉血气水平，每８小时测１次，监测１～７天。结果：３３例患者中有２５例出现脑氧不饱和状态，其中脑充血１９例，脑缺氧６例。创伤程度和颅内压影响ＳｊＯ２，并密切相关（创伤程度：ｒ＝－０．８７７，Ｐ＜０．００１；颅内压：ｒ＝０．４６８，Ｐ＜０．００１）。结论：严重颅脑创伤后，脑充血（脑过度灌注）较为常见，并与颅内压密切相关；ＳｊＯ２增高提示脑过度灌注。重型颅脑伤后若ＳｊＯ２持续０．５０或＞０．７０都表明预后不良。     

Non-invasive estimation of jugular venous oxygen saturation: a comparison between near infrared spectroscopy and transcutaneous venous oximetry

The ability of practitioners to assess the adequacy of global oxygen delivery is dependent on an accurate measurement of central venous saturation. Traditional techniques require the placement of invasive central venous access devices. This study aimed to compare two non-invasive technologies for the estimation of regional venous saturation (reflectance plethysmography and near infrared spectroscopy [NIRS]), using venous blood gas analysis as gold standard. Forty patients undergoing cardiac surgery were recruited in two groups. In the first group a reflectance pulse oximeter probe was placed on the skin overlying the internal jugular vein. In the second group, a Somanetics INVOS oximeter patch was placed on the skin overlying the internal jugular vein and overlying the ipsilateral cerebral hemisphere. Central venous catheters were placed in all patients. Oxygen saturation estimates from both groups were compared with measured saturation from venous blood. Twenty patients participated in each group. Data were analyzed by the limits of agreement technique suggested by Bland and Altman and by linear regression analysis. In the reflectance plethysmography group, the mean bias was 4.27% and the limits of agreement were 58.3 to −49.8% (r² = 0.00, p = 0.98). In the NIRS group the mean biases were 10.8% and 2.0% for the sensors attached over the cerebral hemisphere and over the internal jugular vein, respectively, and the limits of agreement were 33.1 to −11.4 and 19.5 to −15.5% (r² = 0.22, 0.28; p = 0.04, 0.03) for the cerebral hemisphere and internal jugular sites, respectively. While transcutaneous regional oximetry and NIRS have both been used to estimate venous and tissue oxygen saturation non-invasively, the correlation between estimates of ScvO₂ and SxvO₂ were statistically significant for near infrared spectroscopy, but not for transcutaneous regional oximetry. Placement of cerebral oximetry patches directly over the internal jugular vein (as opposed to on the forehead) appeared to approximate internal jugular venous saturation better (lower mean bias and tighter limits of agreement), which suggests this modality may with refinement offer the practitioner additional clinically useful information regarding global cerebral oxygen supply and demand matching.     

Usefulness of venous oxygen saturation in the jugular bulb for the diagnosis of brain death: report of 118 patients

OBJECTIVE: To assess the usefulness of venous oxygen saturation in the jugular bulb (SjO(2)) as a complementary test for the diagnosis of brain death. DESIGN: Prospective observational study. SETTING: Polytrauma intensive care unit (ICU) of an acute-care teaching hospital in Santander, Spain. PATIENTS: We studied 118 (44%) out of 270 patients with severe head injury and intracranial hemorrhage meeting criteria of brain death (lack of cardiac response to atropine, unresponsive apnea, and iso-electric EEG in the absence of shock, hypotension and treatment with muscle relaxants and/or central nervous system (CNS) depressant drugs). MEASUREMENTS AND RESULTS: At the moment at which clinical diagnosis of brain death was made and an iso-electric EEG was obtained, simultaneous oxygen saturation in central venous blood (right atrium) (SvO(2)) and jugular venous bulb (SjO(2)) samples was measured. The ratio between SvO(2) and SjO(2), expressed as CvjO(2) (the so-called central venous-jugular bulb oxygen saturation rate; CvjO(2) = SvO(2)/SjO(2)) was calculated. CvjO(2) less than 1 was obtained in 114 patients [mean (SD): 0.89 (0.02)], whereas CvjO(2) greater than 1 was obtained in only 4 (3.38%). In the group of 152 survivors, a single patient was discharged from the ICU in a vegetative state in which CvjO(2) was below 1. CvjO(2)as a complementary test for the diagnosis of brain death showed 96.6% sensitivity, 99.3% specificity, and 99.1% and 97.4% positive and negative predictive values, respectively. CONCLUSION: Central venous-jugular bulb oxygen saturation rate below 1 together with accepted clinical criteria (unresponsive coma with brainstem areflexia) provides non-invasive assessment of cerebral circulatory arrest that can help to suspect brain death.     

The role of femoral venous pressure and femoral venous oxygen saturation in the setting of intra-abdominal hypertension: a pig model

Femoral venous access is frequently used in critically ill patients. Because raised intra-abdominal pressure (IAP) is also frequently found in this group of patients, we examined the impact of IAP and positive end-expiratory pressure (PEEP) on femoral venous pressure (FVP) and femoral venous oxygen saturation (Sfvo2) in an animal model. Thirteen adult pigs received standardized anesthesia and ventilation. Randomized levels of IAP (3 [baseline], 18, and 26 mmHg) were applied, with levels of PEEP (5, 8, 12, and 15 cmH2O) applied randomly at each IAP level. We measured bladder pressure (IAP), superior vena cava pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, FVP, mixed venous oxygen saturation (Svo2), and Sfvo2. We found that FVP correlated well with IAP (FVP = 4.1 + [0.12 × PEEP] + [1.00 × IAP]; R = 0.89, P < 0.001) with a moderate bias and precision of 5.0 and 3.8 mmHg, respectively. Because the level of agreement did not meet the recommendations of the World Society of Abdominal Compartment Syndrome, FVP cannot currently be recommended to measure IAP, and further clinical trials are warranted. However, a raised FVP should prompt the measurement of the bladder pressure. Femoral venous oxygen saturation did correlate neither with Svo2 nor with abdominal perfusion pressure. Therefore, Sfvo2 is of no clinical use in the setting of raised IAP.     

Prospective evaluation of regional oxygen saturation to estimate central venous saturation in sepsis

Current treatment guidelines for sepsis claim an early goal-directed hemodynamic optimization including fluid resuscitation, use of vasopressors and inotropic agents. We investigated the correlation between the prominent treatment goal central venous saturation (ScvO₂) and the frontal and the thenar regional oxygen saturation (rSO₂) measured by near infrared spectroscopy. Secondary, we examined the value of ScvO₂, lactate levels and rSO₂ as surrogate markers of an impaired tissue oxygenation for outcome prediction in sepsis. This prospective, observational study was performed at the surgical intensive care unit of the University Hospital Giessen. A total of 50 patients with sepsis, severe sepsis or septic shock were included. ScvO₂, rSO₂ and lactate were measured at sepsis diagnosis (baseline), 24 and 48 h, thereafter. We investigated the predictive value of frontal and thenar rSO₂ for a decreased SvcO₂ under 70 %. For survivor and non-survivors ScvO₂, rSO₂ and lactate were analysed. Patients with ScvO₂ >70 % showed a trend to higher levels of fontal rSO₂ (62.81 ± 8.06 vs. 53.54 ± 15.48; p = 0.058). ROC-analysis revealed a minor prediction of a decreased ScvO₂ by frontal rSO₂ levels at baseline (AUC = 0.687; 95 % CI 0.511–0.863; p = 0.047). Combined measurements of lactate and ScvO2 showed significantly elevated mortality for patients with ScvO2 ≥70 % and lactate levels ≥2.5 mmol/l (log rank test p = 0.004). In the group with ScvO₂ <70 % and lactate levels <2.5 mmol/l no patients died during the observation period. Frontal rSO₂ correlates with ScvO₂ but both frontal and thenar rSO2 do not exactly discriminate between patients with high or low ScvO2 in sepsis. The combination of elevated lactate >2.5 mmol/l and ScvO₂ >70 % is highly associated with poor outcome in ICU patients with sepsis, severe sepsis and septic shock.     

Subtype-selective antagonism of N-methyl-D-aspartate receptors by felbamate: insights into the mechanism of action

Felbamate is an anticonvulsant used in the treatment of seizures associated with Lennox-Gastaut syndrome and complex partial seizures that are refractory to other medications. Its unique clinical profile is thought to be due to an interaction with N-methyl-D-aspartate (NMDA) receptors, resulting in decreased excitatory amino acid neurotransmission. To further characterize the interaction between felbamate and NMDA receptors, recombinant receptors expressed in Xenopus oocytes were used to investigate the subtype specificity and mechanism of action. Felbamate reduced NMDA- and glycine-induced currents most effectively at NMDA receptors composed of NR1 and NR2B subunits (IC50 = 0.93 mM), followed by NR1-2C (2.02 mM) and NR1-2A (8.56 mM) receptors. The NR1-2B-selective interaction was noncompetitive with respect to the coagonists NMDA and glycine and was not dependent on voltage. Felbamate enhanced the affinity of the NR1-2B receptor for the agonist NMDA by 3.5-fold, suggesting a similarity in mechanism to other noncompetitive antagonists such as ifenprodil. However, a point mutation at position 201 (E201R) of the epsilon2 (mouse NR2B) subunit that affects receptor sensitivity to ifenprodil, haloperidol, and protons reduced the affinity of NR1-epsilon2 receptors for felbamate by only 2-fold. Furthermore, pH had no effect on the affinity of NR1-2B receptors for felbamate. We suggest that felbamate interacts with a unique site on the NR2B subunit (or one formed by NR1 plus NR2B) that interacts allosterically with the NMDA/glutamate binding site. These results suggest that the unique clinical profile of felbamate is due in part to an interaction with the NR1-2B subtype of NMDA receptor.     

The cobalt-albumin binding assay: insights into its mode of action

BACKGROUND: We previously hypothesized that the N-terminus of human serum albumin (HSA) is altered during ischemic events, thus establishing the foundation for the cobalt-HSA binding assay phenomenon. In this investigation, we attempt to clarify the mode of action of the cobalt-HSA binding assay by direct observations of cobalt binding to HSA. METHODS: High pressure liquid chromatography coupled to positive electrospray ionization mass spectrometry (HPLC/MS) was used to study cobalt binding to HSA in the plasma of patients with and without evidence of myocardial ischemia. RESULTS: Strong binding of cobalt to the N-terminus of HSA occurs at pH>7.0. No differences in cobalt binding to the N-terminus of HSA are observed in ischemic versus non-ischemic patients' plasma despite differences in the cobalt-HSA binding assay. Plasma free cysteine/cystine ratio appears to play a role in the quantitative response of the cobalt-HSA binding assay. CONCLUSIONS: The main determinants of the cobalt-HSA binding assay mechanism of action include but are not limited to: the proportion of intact N-terminus of HSA, HSA concentration, plasma cysteine/cystine ratio, plasma pH, and the state of oxidation of cys34 of HSA. Assay improvements that consider and take these factors into account could lead to an improved cobalt-HSA binding assay with greater clinical utility.     

Prognostic significance of the difference between mixed venous and jugular bulb oxygen saturation in comatose patients resuscitated from a cardiac arrest.

To determine the prognostic significance of the difference between mixed venous and jugular bulb oxygen saturation in survivors and non-survivors of a cardiac arrest, we studied 30 comatose patients (21 non-survivors and 9 survivors) resuscitated from a cardiac arrest. We measured mixed venous oxygen saturation (SmvO2) and jugular bulb oxygen saturation (SjO2) immediately after haemodynamic stabilisation (always within 6 h after cardiac arrest) and 6, 12 and 24 h later. In all patients the SjO2 was about 10% lower than the SmvO2 in the first measurement. In the survivors the SjO2 did not change and remained lower than SmvO2 in eight of nine survivors. However, in the non-survivors the SjO2 increased significantly and was finally higher than the SmvO2 in 12 of 20 patients 24 h after cardiac arrest suggesting a decrease in cerebral oxygen consumption due to extensive loss of functional brain tissue. The positive predictive value of (SmvO2-SjO2) < or = 0 for predicting irreversible brain damage at 24 h after cardiac arrest is 93% and the negative predictive value of (SmvO2-SjO2) > 0 is 53%. Sensitivity and specificity are 65 and 89%, respectively. In a previous study we concluded that early jugular bulb oximetry (within 4 h after cardiac arrest) cannot predict cerebral outcome in comatose patients after cardiac arrest. More studies are needed to clarify the role of prolonged monitoring in the prediction of cerebral outcome after cardiac arrest.     

Relation of cerebral tissue oxygenation index to central venous oxygen saturation in children

OBJECTIVE: To evaluate the relationship between the cerebral tissue oxygenation index measured by near-infrared spectroscopy and central venous oxygen saturation (SvO2) after corrective surgery of congenital heart defects in children. DESIGN: Prospective observational clinical study. SETTING: A tertiary neonatal and paediatric intensive care unit for paediatric cardiology. PATIENTS: Neonates and children consecutively admitted to the paediatric cardiology intensive care unit after corrective surgery of non-cyanotic congenital heart defects. MEASUREMENTS AND RESULTS: Forty-three children were studied. Cerebral tissue oxygenation index, measured non-invasively by near-infrared spectroscopy, was compared to SvO2, measured by a catheter placed in the right atrium, and to haemodynamic and respiratory parameters. Pearson's correlation coefficients and p values were calculated. Simultaneously measured values for SvO2 (62.2+/-9.8%, 39.8-80.4%) and cerebral tissue oxygenation index (56.7+/-8.8%, 35.8-71.2%) showed a significant correlation ( r=0.52, p<0.001). CONCLUSION: Cerebral tissue oxygenation index and SvO2 are not interchangeable parameters, but cerebral tissue oxygenation index reflects the haemodynamic influence on cerebral oxygenation after cardiovascular surgery. Further work is necessary to confirm the clinical role of continuous non-invasive measurement of cerebral tissue oxygenation index with regard to the variations of global systemic oxygen consumption after cardiac surgery in children.     

The pursuit of a high central venous oxygen saturation in sepsis: growing concerns

In this issue of Critical Care, Dutch investigators report that, in a cohort of patients with sepsis/septic shock admitted to three different intensive care units (ICUs), low central venous oxygen saturation (ScvO₂) was uncommon at the time of ICU admission, and hospital mortality was <30%. Their findings, taken together with those of recent reports from Australia and New Zealand (ANZ), raise serious concerns about the utility of early goal directed therapy (EGDT) outside the context of the original trial. Despite inclusion of EGDT into the Surviving Sepsis Guidelines, in response to growing uncertainty, ANZ and US investigators will soon begin randomization of patients into two large multicentre trials comparing EGDT to standard therapy. Until such studies are completed, basing international treatment guidelines on a single centre study performed in what may turn out to be a highly atypical environment would seem premature.     

原位肝移植围术期混合静脉血氧饱和度改变及临床意义

目的 观察原位肝移植围术期混合静脉血氧饱和度（SvO2）的变化及其临床意义。方法 20例终末期肝硬化患者接受原位肝移植术。采用心排仪持续监测围术期SvO2、氧供（DO2）、氧耗（VO2）、氧摄取率（ER02）、体温、心排血量（CO）、平均动脉压（MAP）的变化，分析肝移植围术期SvO2与上述各指标的相关性。结果 SvO2在无肝期前15min较术前增高（P〈O．05），在无肝期30min较无肝期前15min显著降低（P〈0．05），在新肝期30min和术毕较术前均显著增高（P均〈O．05）。机体DO2、VO2在无肝期30min均显著降低（P均〈O、05），而在进入新肝期后均显著增高（P均〈O、05）；ERO2进入新肝期后显著增加（P〈O.05）。SvO2在各时间点均与VO2有显著相关性（P均〈O．05），而与DO2、血红蛋白无相关性（P均〉0．05）；SvO2术前与CO有显著相关性（P〈O．05），其他时间点均无相关性（P均〉O．05）。结论 原位肝移植围术期持续监测SvO2对于改善氧代谢具有重要的临床意义。