Cerebral Oxygen Delivery Research Articles

Cerebral Vasospasm in Critically III Patients with Aneurysmal Subarachnoid Hemorrhage: Does the Evidence Support the Ever-Growing List of Potential Pharmacotherapy Interventions?

The occurrence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a significant event resulting in decreased cerebral blood flow and oxygen delivery. Prevention and treatment of cerebral vasospasm is vital to avert neurological damage and reduced functional outcomes. A variety of pharmacotherapy interventions for the prevention and treatment of cerebral vasospasm have been evaluated. Unfortunately, very few large randomized trials exist to date, making it difficult to make clear recommendations regarding the efficacy and safety of most pharmacologic interventions. Considerable debate exists regarding the efficacy and safety of hypervolemia, hemodilution, and hypertension (triple-H therapy), and the implementation of each component varies substantially amongst institutions. There is a new focus on euvolemic-induced hypertension as a potentially preferred mechanism of hemodynamic augmentation. Nimodipine is the one pharmacologic intervention that has demonstrated favorable effects on patient outcomes and should be routinely administered unless contraindications are present. Intravenous nicardipine may offer an alternative to oral nimodipine. The addition of high-dose magnesium or statin therapy has shown promise, but results of ongoing large prospective studies are needed before they can be routinely recommended. Tirilazad and clazosentan offer new pharmacologic mechanisms, but clinical outcome results from prospective randomized studies have largely been unfavorable. Locally administered pharmacotherapy provides a targeted approach to the treatment of cerebral vasospasm. However, the paucity of data makes it challenging to determine the most appropriate therapy and implementation strategy. Further studies are needed for most pharmacologic therapies to determine whether meaningful efficacy exists.

Brain tissue oxygenation, lactate-pyruvate ratio, and cerebrovascular pressure reactivity monitoring in severe traumatic brain injury: systematic review and viewpoint.

Prevention and detection of secondary brain insults via multimodality neuromonitoring is a major goal in patients with severe traumatic brain injury (TBI). Explore the underlying pathophysiology and clinical outcome correlates as it pertains to combined monitoring of ≥2 from the following variables: partial brain tissue oxygen tension (PbtO(2)), pressure reactivity index (PRx), and lactate pyruvate ratio (LPR). Data sources included Medline, EMBASE, and evidence-based databases (Cochrane DSR, ACP Journal Club, DARE, and the Cochrane Controlled Trials Register). The PRISMA recommendations were followed. Two authors independently selected articles meeting inclusion criteria. Studies enrolled adults who required critical care and monitoring in the setting of TBI. Included studies reported on correlations between the monitored variables and/or reported on correlations of the variables with clinical outcomes. Thirty-four reports were included (32 observational studies and 2 randomized controlled trials) with a mean sample size of 34 patients (range 6-223), and a total of 1,161 patient-observations. Overall methodological quality was moderate. Due to inter-study heterogeneity in outcomes of interest, study design, and in both number and type of covariates included in multivariable analyses, quantitative synthesis of study results was not undertaken. Several literature limitations were identified including small number of subjects, lack of clinical outcome correlations, inconsistent probe location, and overall moderate quality among the included studies. These limitations preclude any firm conclusions; nevertheless we suggest that the status of cerebrovascular reactivity is not only important for cerebral perfusion pressure optimization but should also inform interpretation and interventions targeted on PbtO(2) and LPR. Assessment of reactivity can be the first step in approaching the relations among cerebral blood flow, oxygen delivery, demand, and cellular metabolism.

A Feasibility Study of Cerebral Oximetry During In-Hospital Mechanical and Manual Cardiopulmonary Resuscitation*

A major hurdle limiting the ability to improve the quality of resuscitation has been the lack of a noninvasive real-time detection system capable of monitoring the quality of cerebral and other organ perfusion, as well as oxygen delivery during cardiopulmonary resuscitation. Here, we report on a novel system of cerebral perfusion targeted resuscitation. An observational study evaluating the role of cerebral oximetry (Equanox; Nonin, Plymouth, MI, and Invos; Covidien, Mansfield, MA) as a real-time marker of cerebral perfusion and oxygen delivery together with the impact of an automated mechanical chest compression system (Life Stat; Michigan Instruments, Grand Rapids, MI) on oxygen delivery and return of spontaneous circulation following in-hospital cardiac arrest. Tertiary medical center. In-hospital cardiac arrest patients (n = 34). Cerebral oximetry provided real-time information regarding the quality of perfusion and oxygen delivery. The use of automated mechanical chest compression device (n = 12) was associated with higher regional cerebral oxygen saturation compared with manual chest compression device (n = 22) (53.1% ± 23.4% vs 24% ± 25%, p = 0.002). There was a significant difference in mean regional cerebral oxygen saturation (median % ± interquartile range) in patients who achieved return of spontaneous circulation (n = 15) compared with those without return of spontaneous circulation (n = 19) (47.4% ± 21.4% vs 23% ± 18.42%, p < 0.001). After controlling for patients achieving return of spontaneous circulation or not, significantly higher mean regional cerebral oxygen saturation levels during cardiopulmonary resuscitation were observed in patients who were resuscitated using automated mechanical chest compression device (p < 0.001). The integration of cerebral oximetry into cardiac arrest resuscitation provides a novel noninvasive method to determine the quality of cerebral perfusion and oxygen delivery to the brain. The use of automated mechanical chest compression device during in-hospital cardiac arrest may lead to improved oxygen delivery and organ perfusion.

AltitudeOmics: the effect of high altitude ascent and acclimatisation on cerebral blood flow regulation (885.1)

Adequate oxygen supply to the brain is critical to maintain brain function. Hypoxia presents a unique challenge in maintaining sufficient cerebral oxygen delivery (DO2). We assessed by ultrasound cerebral blood flow (CBF: internal carotid, vertebral arteries and middle cerebral artery velocity [MCAv]) and arterial blood pressure (index of cerebral autoregulation; CA) during rest and hypercapnic breathing (MCAv‐CO2 slope; index of cerebrovascular function) in 21 healthy subjects at sea‐level (SL) and upon arrival at 5260m (ALT1) and after 16 days of acclimatisation (ALT16). Cerebral DO2 was calculated as the product of arterial oxygen content (CaO2) and flow in each respective artery and summed to estimate global CBF. Global CBF increased ~70% upon arrival at ALT1 (P&lt;0.05) and returned to SL values at ALT16 as a result of changes in cerebral vascular resistance. A reciprocal pattern in CaO2 maintained global cerebral DO2 across acclimatisation. MCAv‐CO2 slope was elevated by ~79% upon arrival at ALT1 and further increased by ~89% at ALT16 (P&lt;0.05). Indexes of CA were reduced upon arrival at ALT1 (P&lt;0.05), but did not change with acclimatisation at ALT16 (P&gt;0.10). Cerebral DO2 was well maintained upon acute exposure and acclimatisation to hypoxia. Cerebrovascular function was enhanced with acclimatisation to high altitude, but these changes did not mitigate the reduction in CA associated with hypoxic exposure.Grant Funding Source: Supported by U.S. Department of Defense

AltitudeOmics: effect of ascent and acclimatization to 5260 m on regional cerebral oxygen delivery

Cerebral hypoxaemia associated with rapid ascent to high altitude can be life threatening; yet, with proper acclimatization, cerebral function can be maintained well enough for humans to thrive. We investigated adjustments in global and regional cerebral oxygen delivery (DO2) as 21 healthy volunteers rapidly ascended and acclimatized to 5260m. Ultrasound indices of cerebral blood flow in internal carotid and vertebral arteries were measured at sea level, upon arrival at 5260m (ALT1; atmospheric pressure 409mmHg) and after 16days of acclimatization (ALT16). Cerebral DO2 was calculated as the product of arterial oxygen content and flow in each respective artery and summed to estimate global cerebral blood flow. Vascular resistances were calculated as the quotient of mean arterial pressure and respective flows. Global cerebral blood flow increased by ∼70% upon arrival at ALT1 (P<0.001) and returned to sea-level values at ALT16 as a result of changes in cerebral vascular resistance. A reciprocal pattern in arterial oxygen content maintained global cerebral DO2 throughout acclimatization, although DO2 to the posterior cerebral circulation was increased by ∼25% at ALT1 (P=0.032). We conclude that cerebral DO2 is well maintained upon acute exposure and acclimatization to hypoxia, particularly in the posterior and inferior regions of the brain associated with vital homeostatic functions. This tight regulation of cerebral DO2 was achieved through integrated adjustments in local vascular resistances to alter cerebral perfusion during both acute and chronic exposure to hypoxia.

Time Course Variations in the Mechanisms by Which Cerebral Oxygen Delivery Is Maintained on Exposure to Hypoxia/Altitude

Normal cerebral function is dependent upon an adequate and continuous supply of oxygen. This study calculated cerebral blood flow based on assessment of the right middle cerebral artery (MCA) velocity (MCAVel) and MCA diameter (MCADiam) by trans-cranial Doppler and trans-cranial Duplex in normoxia, during acute exposure to 12% normobaric hypoxia for up to 6 hours, and after 3 days exposure to the equivalent altitude, 4392 m, in nine subjects. Mean (SD) MCAVel increased both after 6 hours hypoxia from 76.8 (11.4) to 97.2 (17.4) cms/sec (p<0.001), and after 3 days at altitude from 68.1 (7.5) [sea level] to 76.2 (10.2) [4392 m] (p=0.015). MCADiam increased from 5.07 (0.6) to 6.1 (0.6) mm (p<0.001) after 6 hours of 12% hypoxia. Calculated mean MCA blood flow increased after 6 hours of 12% hypoxia from 5.0 (0.6) mL/sec to 8.9 (1.2) mL/sec, but there was no difference between sea level and 4392 m. Calculated mean cerebral oxygen delivery increased from 72.4 (14.4) to 107 (20.1) mL/sec (p<0.001) after 6 hours of 12% hypoxia and was maintained unchanged at 4392 m. An increase in MCA caliber, rather than blood velocity, was a major contributor to increased oxygen delivery accompanying within the first few hours of exposure to acute hypoxia. During more long-term exposure, increases in MCA velocity and a rise in hemoglobin appeared to be the more important mechanisms in maintaining cerebral oxygen delivery. The implication of this observed change in MCA diameter questions the widely held assumption that MCA velocity is a surrogate for flow during acute hypoxic exposure.

Moderate Hyperventilation during Intravenous Anesthesia Increases Net Cerebral Lactate Efflux

Hyperventilation is known to decrease cerebral blood flow (CBF) and to impair cerebral metabolism, but the threshold in patients undergoing intravenous anesthesia is unknown. The authors hypothesized that reduced CBF associated with moderate hyperventilation might impair cerebral aerobic metabolism in patients undergoing intravenous anesthesia. Thirty male patients scheduled for coronary surgery were included in a prospective, controlled crossover trial. Measurements were performed under fentanyl-midazolam anesthesia in a randomized sequence aiming at partial pressures of carbon dioxide of 30 and 50 mmHg. Endpoints were CBF, blood flow velocity in the middle cerebral artery, and cerebral metabolic rates for oxygen, glucose, and lactate. Global CBF was measured using a modified Kety-Schmidt technique with argon as inert gas tracer. CBF velocity of the middle cerebral artery was recorded by transcranial Doppler sonography. Data were presented as mean (SD). Two-sided paired t tests and one-way ANOVA for repeated measures were used for statistical analysis. Moderate hyperventilation significantly decreased CBF by 60%, blood flow velocity by 41%, cerebral oxygen delivery by 58%, and partial pressure of oxygen of the jugular venous bulb by 45%. Cerebral metabolic rates for oxygen and glucose remained unchanged; however, net cerebral lactate efflux significantly increased from -0.38 (2.18) to -2.41(2.43) µmol min 100 g. Moderate hyperventilation, when compared with moderate hypoventilation, in patients with cardiovascular disease undergoing intravenous anesthesia increased net cerebral lactate efflux and markedly reduced CBF and partial pressure of oxygen of the jugular venous bulb, suggesting partial impairment of cerebral aerobic metabolism at clinically relevant levels of hypocapnia.

Stability of cerebral metabolism and substrate availability in humans during hypoxia and hyperoxia

Characterization of the influence of oxygen availability on brain metabolism is an essential step toward a better understanding of brain energy homoeostasis and has obvious clinical implications. However, how brain metabolism depends on oxygen availability has not been clearly examined in humans. We therefore assessed the influence of oxygen on CBF (cerebral blood flow) and CMRO2 (cerebral metabolic rates for oxygen) and carbohydrates. PaO2 (arterial partial pressure of oxygen) was decreased for 15min to ~60, ~44 and ~35 mmHg [to target a SaO2 (arterial oxygen saturation) of 90, 80 and 70% respectively], and elevated to ~320 and ~430 mmHg. Isocapnia was maintained during each trial. At the end of each stage, arterial-jugular venous differences and volumetric CBF were measured to directly calculate cerebral metabolic rates. During progressive hypoxaemia, elevations in CBF were correlated with the reductions in both SaO2 (R2=0.54, P<0.05) and CaO2 (arterial oxygen content) (R2=0.57, P<0.05). Despite markedly reduced CaO2, cerebral oxygen delivery was maintained by increased CBF. Cerebral metabolic rates for oxygen, glucose and lactate remained unaltered during progressive hypoxia. Consequently, cerebral glucose delivery was in excess of that required, and net lactate efflux increased slightly in severe hypoxia, as reflected by a small increase in jugular venous lactate. Progressive hyperoxia did not alter CBF, CaO2, substrate delivery or cerebral metabolism. In conclusion, marked elevations in CBF with progressive hypoxaemia and related reductions in CaO2 resulted in a well-maintained cerebral oxygen delivery. As such, cerebral metabolism is still supported almost exclusively by carbohydrate oxidation during severe levels of hypoxaemia.

Neuroprotective strategies--what do we really need to know?

While preliminary data are encouraging, definitive data are lacking to conclusively demonstrate the benefit of perioperative neurologic monitoring in improving neurodevelopmental outcomes in children who require surgery for congenital heart disease. Nonetheless, in the current era, some form of perioperative neurologic monitoring is important. Strategies include bicortical near infrared spectroscopy monitoring in the pre- and postoperative periods along with bicortical near infrared spectroscopy and transcranial Doppler intraoperatively. These monitors provide real-time information concerning cerebral oxygen delivery and blood flow. These strategies will allow us to refine treatments to optimize neurodevelopmental potential in children with congenital heart disease.

A note on arterial to venous oxygen saturation as reference for NIRS-determined frontal lobe oxygen saturation in healthy humans

A note on arterial to venous oxygen saturation as reference for NIRS-determined frontal lobe oxygen saturation in healthy humans

Early Cerebral Oxygen Extraction and the Risk of Death or Sonographic Brain Injury in Very Preterm Infants

To evaluate the relationship between cerebral fractional tissue oxygen extraction (cFTOE), a measure of oxygen delivery-consumption equilibrium, and the risk of early poor outcome in very preterm infants. Cerebral blood flow, tissue oxygenation index (by near-infrared spectroscopy), and arterial oxygen content were measured, and cerebral oxygen delivery, consumption, and cFTOE were calculated at 3 intervals in the first 72 hours of life in infants ≤ 30 weeks gestational age (GA). A receiver operating characteristic curve was derived with an a priori defined dichotomized outcome of good or poor, defined as death or sonographic brain injury (grade ≥ II intraventricular hemorrhage) by day 7. Seventy-one infants were enrolled, with a mean (SD) GA of 27 (2) weeks. cFTOE demonstrated better discrimination for the study outcome at <24 hours of age than at 48 or 72 hours of age (P = .01). The area under the curve for cFTOE at the initial measurement was no different from that for GA alone (0.87; 95% CI, 0.77-0.95 vs 0.81; 95% CI, 0.69-0.92), but the combined measure of cFTOE and GA had better discrimination (0.96; 95% CI, 0.91-1.0) than either cFTOE (P = .03) or GA (P = .016) alone. A cFTOE of 0.4 had a sensitivity of 82% and specificity of 75% for risk of early poor outcome. Elevated cFTOE values are associated with increased risk of early poor outcome in very preterm infants. Its predictive value is further improved with the addition of GA.

A feasibility study of cerebral oximetry monitoring during the post-resuscitation period in comatose patients following cardiac arrest

BackgroundOne of the major causes of death and neurological injury after cardiac arrest is delayed ischemia combined with oxygen free radical mediated reperfusion injury. Consequently determining the optimal balance between oxygen delivery and uptake in the brain using a reliable non-invasive monitoring system during the post-resuscitation period is of importance. In this observational study, we evaluated the feasibility of using cerebral oximetry during the post-resuscitation period in order to identify changes in regional cerebral oxygen saturation (rSO2) and its association with survival to discharge. Methods21 consecutive patients admitted to the intensive care units following cardiac arrest had cerebral oximetry monitoring carried out for 48h. Mean rSO2 values were collected during the first 24h and then again during the subsequent 24–48h of the post-resuscitation period. Results43% (n=9) patients survived to hospital discharge and 57% (n=12) died. Amongst all patients the median (IQR) rSO2% was 65.5% (62.6–68.2) in the first 24-h following ROSC and increased to 72.1% (64.6–73.7) (p=0.11) in the subsequent 24–48h. The median (IQR) rSO2% during the first 24h in patients who survived to discharge compared to those who did not survive were significantly higher 68.2% (66.0–71.0) vs. 62.9% (56.5–66.0), p=0.01). During the subsequent 24–48h period, while a difference in the rSO2 between survivors and non-survivors was noted, this did not achieve statistical significance (median (IQR): 73.7 (70.2–74.0) vs. 66.5 (58.2–72.1), p=0.11). ConclusionsOur study indicates that the use of cerebral oximetry is feasible during the post resuscitation period after cardiac arrest. Further studies are needed to determine whether cerebral oximetry may be used as a novel non-invasive monitoring system to evaluate changes in the balance between cerebral oxygen delivery and uptake during the post-resuscitation period.

Cerebral Blood Flow and Oxygen Delivery In Response To Hyperoxia In Sickle Cell Anemia

Neurovascular sequalae are a common occurrence in Sickle Cell Anemia (SCA), with 11% of patients suffering cerebral vascular accident (CVA), or overt stroke by their twentieth birthday and 40% of patients developing silent cerebral infarcts (SCI) by age 14. Elevated transcranial Doppler (TCD) velocity of the middle cerebral artery identifies patients at risk for stroke, and this risk can be reduced by chronic transfusion therapy. However, the specificity of TCD is low causing many patients to be transfused unnecessarily. To further refine cerebrovascular risk stratification, we are studying factors responsible for normal and pathophysiologic cerebral blood flow (CBF) in SCD patients. Cerebral blood flow is increased in SCA patients compared to controls, but is believed to be a compensatory mechanism for chronic anemia and systemic desaturation. In order to test this hypothesis, we studied whole CBF and oxygen delivery (DO2) at rest and in response to hyperoxia in subjects with SCA and sickle cell trait (SCT).All patients were recruited at Children's Hospital Los Angeles through an IRB approved protocol. Informed consent was obtained for all patients. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month. EKG, peripheral arterial oxygen saturation (SaO2), and fractional inspired oxygen (fiO2) were measured continuously throughout the study. Imaging consisted of a survey, reference scan, angiography localization, and nine axial phase contrast (PC) images. PC slices were placed inferior to the Circle of Willis, perpendicular to the carotids and basilar arteries. Participants received room air and 100% O2 through a non rebreathing respiratory circuit at 10 L/m. Room air exposure 20 minutes with six PC images collected throughout. Oxygen was delivered for 5 minutes followed by three more PC images. Blood for hemoglobin (HGB) and hematocrit (HCT) were drawn prior to MRI testing. No adverse events were reported upon follow up.Nine patients with SCA (5 male, 22.5 ± 6.7 yo p<0.05) and 3 with sickle cell trait (2 male, 36.7 ± 8.7 yo p<0.05) were studied. Baseline HGB was 25% lower (9.7 ± 1.3 versus 12.9 ± 0.1) and baseline HCT was 41% lower (28.0 ± 3.6 versus 47.3 ± 0.14 SCT) in SCA patients (p<0.05). Baseline whole brain CBF was elevated in SCA (1398 ± 400 ml/min versus 700 ± 172 ml/min). After correcting for HGB and SaO2, DO2 remained higher in SCA (192 ± 75 ml/min versus 105 ± 1.4 ml/min, p<0.05). During hyperoxia, whole brain CBF decreased by 10-15%, but the change was proportional to increased oxygen carrying capacity such that there was no change in DO2 in either populations.The increase in CBF we observed in SCA patients has been described using other modalities. However, we are the first to demonstrate that the increased flow observed is almost double what can be explained by their anemia and arterial desaturation alone. There are several possibilities for this observation. 1) SCA patients could have increased cerebral metabolic rate. If so, their mixed cerebral venous saturation will be normal and the flow is appropriate; 2) SCA patients have a mismatch between cerebral perfusion and metabolic demand, whether much of the increased flow does not effectively unload oxygen. If so, cerebral venous saturation would be high. We are currently optimizing MRI and NIR's technologies to estimate cerebrovascular metabolic rate, mixed cerebral venous saturation, and local supply-demand balance. [Display omitted] [Display omitted] Disclosures:Coates:Novartis Inc.: Honoraria, Speakers Bureau; Apopharma: Honoraria, Speakers Bureau; Shire: Speakers Bureau. Wood:Shire: Consultancy, Research Funding; Apopharma: Honoraria, Patents & Royalties; Novartis: Honoraria.

Cerebral blood flow in the neonate

Ensuring adequate oxygenation of the developing brain is the cornerstone of neonatal critical care. Despite decades of clinical research dedicated to this issue of paramount importance, our knowledge and understanding regarding the physiology and pathophysiology of neonatal cerebral blood flow are still rudimentary. This review primarily focuses on currently available human clinical and experimental data on cerebral blood flow and autoregulation in the preterm and term infant. Limitations of systemic blood pressure values as surrogates for monitoring adequate cerebral oxygen delivery are discussed. Particular emphasis is placed on the high interindividual variability in cerebral blood flow values, vasoreactivity, and autoregulatory thresholds making the applications of normative values highly questionable. Technical and ethical difficulties to conduct such trials leave us with a near complete lack of knowledge on how pharmacological and surgical interventions impact on cerebral autoregulation. The ensemble of these works argues for the necessity of highly individualized care by taking advantage of continuous bedside monitoring of cerebral circulation. They also point to the urgent need for further studies addressing the exciting but difficult issue of cerebral blood flow autoregulation in the neonate.

Transcranial doppler and near infrared spectroscopy in the perioperative period

Maintenance of adequate blood flow and oxygen to the brain is one of the principal endpoints of all surgery and anesthesia. During operations in general anesthesia, however, the brain is at particular risk for silent ischemia. Despite this risk, the brain still remains one of the last monitored organs in clincial anesthesiology. Transcranial Doppler (TCD) sonography and near-infrared spectroscopy (NIRS) experience a revival as these noninvasive technologies help to detect silent cerebral ischemia. TCD allows for quantification of blood flow velocities in basal intracranial arteries. TCD-derived variables such as the pulsatility index might hint toward diminished cognitive reserve or raised intracranial pressure. NIRS allows for assessment of regional cerebral oxygenation. Monitoring should be performed during high-risk surgery for silent cerebral ischemia and special circumstances during critical care medicine. Both techniques allow for the assessment of cerebrovascular autoregulation and individualized management of cerebral hemodynamics. TCD and NIRS are noninvasive monitors that anesthesiologists apply to tailor cerebral oxygen delivery, aiming to safeguard brain function in the perioperative period.

A pilot study examining the role of regional cerebral oxygen saturation monitoring as a marker of return of spontaneous circulation in shockable (VF/VT) and non-shockable (PEA/Asystole) causes of cardiac arrest

BackgroundNon-invasive monitoring of cerebral perfusion and oxygen delivery during cardiac arrest is not routinely utilized during cardiac arrest resuscitation. The objective of this study was to investigate the feasibility of using cerebral oximetry during cardiac arrest and to determine the relationship between regional cerebral oxygen saturation (rSO2) with return of spontaneous circulation (ROSC) in shockable (VF/VT) and non-shockable (PEA/asystole) types of cardiac arrest. MethodsCerebral oximetry was applied to 50 in-hospital and out-of-hospital cardiac arrest patients. ResultsOverall, 52% (n=26) achieved ROSC and 48% (n=24) did not achieve ROSC. There was a significant difference in mean±SD rSO2% in patients who achieved ROSC compared to those who did not (47.2±10.7% vs. 31.7±12.8%, p<0.0001). This difference was observed during asystole (median rSO2 (IQR) ROSC versus no ROSC: 45.0% (35.1–48.8) vs. 24.9% (20.5–32.9), p<0.002) and PEA (50.6% (46.7–57.5) vs. 31.6% (18.8–43.3), p=0.02), but not in the VF/VT subgroup (43.7% (41.1–54.7) vs. 42.8% (34.9–45.0), p=0.63). Furthermore, it was noted that no subjects with a mean rSO2<30% achieved ROSC. ConclusionsCerebral oximetry may have a role as a real-time, non-invasive predictor of ROSC during cardiac arrest. The main utility of rSO2 in determining ROSC appears to apply to asystole and PEA subgroups of cardiac arrest, rather than VF/VT. This observation may reflect the different physiological factors involved in recovery from PEA/asytole compared to VF/VT. Whereas in VF/VT, successful defibrillation is of prime importance, however in PEA and asytole achieving ROSC is more likely to be related to the quality of oxygen delivery. Furthermore, a persistently low rSO2 <30% in spite of optimal resuscitation methods may indicate futility of resuscitation efforts.

Hypotension in Newborn Infants and Its Treatment

Systemic hypotension is a common complication of sick premature infants and may be associated with major adverse outcomes, including intraventricular hemorrhage, neurodevelopmental morbidity, and mortality. There is no consensus among neonatologists regarding either the definition of hypotension or the lower threshold level of systemic arterial blood pressure in which neurological injury is inevitable. For this reason, there is a considerable variation in the reported prevalence of hypotension among different neonatal units. However, it is widely accepted by many of clinicians that early and aggressive treatment of hypotension in the neonates leads to improved neurologic outcome and survival. The goal of treatment of hypotension is to maintain adequate organ blood flow, particularly, cerebral blood flow. Because of difficulties in evaluating organ perfusion and adequacy of cerebral oxygen delivery, treatment decisions are based on statistically defined gestational and postnatal agedependent normative blood-pressure values combined with clinical intuition. Current treatment of hypotension in the premature infant includes the use of volume expansions, inotropes, vasopressor agents and corticosteroids. It has been reported that dopamine, as a commonly used inotropic agents in the neonatal period, is more effective than dobutamine in the raising of blood pressure. Some hypotensive premature infants have low cortisol levels because of adrenocortical insufficiency, and corticosteroids are generally reserved for treatment of refractory hypotension of these infants; however, it is not recommended for prophylaxis or routine clinical use because of its potential serious side effects. This article aims to review some of the controversies about diagnosis and management of systemic hypotension in the newborn infants

The SafeBoosC Phase II Randomised Clinical Trial: A Treatment Guideline for Targeted Near-Infrared-Derived Cerebral Tissue Oxygenation versus Standard Treatment in Extremely Preterm Infants

Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rSt<smlcap>O</smlcap>₂) reflects venous oxygen saturation. If cerebral metabolism is stable, rSt<smlcap>O</smlcap>₂ can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the burden of hypo- and hyperoxia can be reduced by the combined use of close monitoring of the cerebral rSt<smlcap>O</smlcap>₂ and a treatment guideline to correct deviations in rSt<smlcap>O</smlcap>₂ outside a predefined target range. Aims: To describe the rationale for and content of this treatment guideline. Methods: Review of the literature and assessment of the quality of evidence and the grade of recommendation for each of the interventions. Results and Conclusions: A clinical intervention algorithm based on the main determinants of cerebral perfusion-oxygenation changes during the first hours after birth was generated. The treatment guideline is presented to assist neonatologists in making decisions in relation to cerebral oximetry readings in preterm infants within the SafeBoosC phase II randomised clinical trial. The evidence grades were relatively low and the guideline cannot be recommended outside a research setting.

Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury

Monitoring and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is a standard of care after traumatic brain injury (TBI). However, the pathophysiology of so-called secondary brain injury, i.e., the cascade of potentially deleterious events that occur in the early phase following initial cerebral insult—after TBI, is complex, involving a subtle interplay between cerebral blood flow (CBF), oxygen delivery and utilization, and supply of main cerebral energy substrates (glucose) to the injured brain. Regulation of this interplay depends on the type of injury and may vary individually and over time. In this setting, patient management can be a challenging task, where standard ICP/CPP monitoring may become insufficient to prevent secondary brain injury. Growing clinical evidence demonstrates that so-called multimodal brain monitoring, including brain tissue oxygen (PbtO2), cerebral microdialysis and transcranial Doppler among others, might help to optimize CBF and the delivery of oxygen/energy substrate at the bedside, thereby improving the management of secondary brain injury. Looking beyond ICP and CPP, and applying a multimodal therapeutic approach for the optimization of CBF, oxygen delivery, and brain energy supply may eventually improve overall care of patients with head injury. This review summarizes some of the important pathophysiological determinants of secondary cerebral damage after TBI and discusses novel approaches to optimize CBF and provide adequate oxygen and energy supply to the injured brain using multimodal brain monitoring.

Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin

The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy (Δ[oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the Δ[oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of Δ[oxCCO] as well as of concentration changes in oxygenated (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in Δ[oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the Δ[oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the Δ[oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived Δ[oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin.