Dynamics of Critical Closing Pressure Explain Cerebral Autoregulation Impairment in Acute Cerebrovascular Disease.

INTRODUCTION: Cerebral autoregulation (CA) is impaired in acute ischemic stroke (AIS) and is associated with worse patient outcomes, but the underlying physiological cause is unclear. This study tests whether depressed CA in AIS can be linked to the dynamic responses of critical closing pressure (CrCP) and resistance area product (RAP). METHODS: Continuous recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), arterial blood pressure (BP), end-tidal CO2 and electrocardiography allowed dynamic analysis of the instantaneous MCAv-BP relationship to obtain estimates of CrCP and RAP. The dynamic response of CrCP and RAP to a sudden change in mean BP was obtained by transfer function analysis. Comparisons were made between younger controls (≤50 years), older controls (>50 years), and AIS patients. RESULTS: Data from 24 younger controls (36.4 ± 10.9 years, 9 male), 38 older controls (64.7 ± 8.2 years, 20 male), and 20 AIS patients (63.4 ± 13.8 years, 9 male) were included. Dynamic CA was impaired in AIS, with lower autoregulation index (affected hemisphere: 4.0 ± 2.3, unaffected: 4.5 ± 1.8) compared to younger (right: 5.8 ± 1.4, left: 5.8 ± 1.4) and older (right: 4.9 ± 1.6, left: 5.1 ± 1.5) controls. AIS patients also demonstrated an early (0-3 s) peak in CrCP dynamic response that was not influenced by age. CONCLUSION: These early transient differences in the CrCP dynamic response are a novel finding in stroke and occur too early to reflect underlying regulatory mechanisms. Instead, these may be caused by structural changes to cerebral vasculature.

The prediction of estimated cerebral perfusion pressure with trans-systolic time in preterm and term infants.

It is important to monitor cerebral perfusion in infants because hypo- and hyperperfusion can contribute to neurological injury. This study aimed to clarify the relationship between trans-systolic time (TST) and critical closing pressure (CrCP) or estimated cerebral perfusion pressure (CPPe) in neonates. Moreover, we aimed to determine the TST values in preterm and term infants with stable cerebral perfusion to clarify normative reference data. This multicentre prospective study included infants with arterial lines admitted to the neonatal intensive care units between December 2021 and August 2023. TST, CrCP, and CPPe were calculated using middle cerebral artery waveforms recorded using transcranial Doppler ultrasonography when clinicians collected arterial blood samples. Three hundred and sixty samples were obtained from 112 infants with a gestational age of 32 (interquartile range, 27-37) weeks and a birth weight of 1481 (956-2355) g. TST was positively correlated with CPPe (r = 0.60, p < 0.001), but not with CrCP (r = 0.08, p = 0.10). The normative reference values of TST in preterm and term infants without samples of hyper- or hypocapnia and/or hyper- or hypotension, which may affect cerebral perfusion, were as follows: ≤ 29 weeks, 0.12 (0.11-0.14) s; 30-36 weeks, 0.14 (0.12-0.15) s; and ≥ 37 weeks, 0.16 (0.14-0.17) s, respectively.  Conclusion: TST in neonates significantly correlated with CPPe, but not with CrCP. TST may be a good predictor of cerebral perfusion and potentially have wider clinical applications. What is Known: • Trans-systolic time (TST) is used in evaluating the effects of increased intracranial pressure on cerebral haemodynamics. However, little is known about the efficacy of TST in predicting neonatal cerebral perfusion pressure. What is New: • This study added evidence that TST correlated with estimated cerebral perfusion pressure, but not with critical closing pressure. Additionally, we showed the normative reference values of the TST in preterm and term infants.

Critical Closing Pressure and Cerebrovascular Resistance Responses to Intracranial Pressure Variations in Neurocritical Patients.

BACKGROUND: Critical closing pressure (CrCP) and resistance-area product (RAP) have been conceived as compasses to optimize cerebral perfusion pressure (CPP) and monitor cerebrovascular resistance, respectively. However, for patients with acute brain injury (ABI), the impact of intracranial pressure (ICP) variability on these variables is poorly understood. The present study evaluates the effects of a controlled ICP variation on CrCP and RAP among patients with ABI. METHODS: Consecutive neurocritical patients with ICP monitoring were included along with transcranial Doppler and invasive arterial blood pressure monitoring. Internal jugular veins compression was performed for 60 s for the elevation of intracranial blood volume and ICP. Patients were separated in groups according to previous intracranial hypertension severity, with either no skull opening (Sk1), neurosurgical mass lesions evacuation, or decompressive craniectomy (DC) (patients with DC [Sk3]). RESULTS: Among 98 included patients, the correlation between change (Δ) in ICP and the corresponding ΔCrCP was strong (group Sk1 r = 0.643 [p = 0.0007], group with neurosurgical mass lesions evacuation r = 0.732 [p < 0.0001], and group Sk3 r = 0.580 [p = 0.003], respectively). Patients from group Sk3 presented a significantly higher ΔRAP (p = 0.005); however, for this group, a higher response in mean arterial pressure (change in mean arterial pressure p = 0.034) was observed. Exclusively, group Sk1 disclosed reduction in ICP before internal jugular veins compression withholding. CONCLUSIONS: This study elucidates that CrCP reliably changes in accordance with ICP, being useful to indicate ideal CPP in neurocritical settings. In the early days after DC, cerebrovascular resistance seems to remain elevated, despite exacerbated arterial blood pressure responses in efforts to maintain CPP stable. Patients with ABI with no need of surgical procedures appear to remain with more effective ICP compensatory mechanisms when compared with those who underwent neurosurgical interventions.

Prolonged Automated Robotic TCD Monitoring in Acute Severe TBI: Study Design and Rationale.

BACKGROUND: Transcranial Doppler ultrasonography (TCD) is a portable, bedside, noninvasive diagnostic tool used for the real-time assessment of cerebral hemodynamics. Despite the evident utility of TCD and the ability of this technique to function as a stethoscope to the brain, its use has been limited to specialized centers because of the dearth of technical and clinical expertise required to acquire and interpret the cerebrovascular parameters. Additionally, the conventional pragmatic episodic TCD monitoring protocols lack dynamic real-time feedback to guide time-critical clinical interventions. Fortunately, with the recent advent of automated robotic TCD technology in conjunction with the automated software for TCD data processing, we now have the technology to automatically acquire TCD data and obtain clinically relevant information in real-time. By obviating the need for highly trained clinical personnel, this technology shows great promise toward a future of widespread noninvasive monitoring to guide clinical care in patients with acute brain injury. METHODS: Here, we describe a proposal for a prospective observational multicenter clinical trial to evaluate the safety and feasibility of prolonged automated robotic TCD monitoring in patients with severe acute traumatic brain injury (TBI). We will enroll patients with severe non-penetrating TBI with concomitant invasive multimodal monitoring including, intracranial pressure, brain tissue oxygenation, and brain temperature monitoring as part of standard of care in centers with varying degrees of TCD availability and experience. Additionally, we propose to evaluate the correlation of pertinent TCD-based cerebral autoregulation indices such as the critical closing pressure, and the pressure reactivity index with the brain tissue oxygenation values obtained invasively. CONCLUSIONS: The overarching goal of this study is to establish safety and feasibility of prolonged automated TCD monitoring for patients with TBI in the intensive care unit and identify clinically meaningful and pragmatic noninvasive targets for future interventions.

Myoelectric characteristics of tensor palatini and collapsibility of upper airway in OSA patients with different phenotypes under DISE.

OBJECTIVE: This study aims to evaluate the combination of myoelectric characteristics of tensor palatini muscle (TP) and collapsibility of upper airway in obstructive sleep apnea (OSA) patients with different external phenotypes of collapse pattern at velum level under drug-induced sleep endoscopy (DISE). STUDY DESIGN: Case series with planned data collection. SETTING: Operation room. SUBJECTS AND METHODS: 36 mainly collapse pattern at velum level OSA subjects underwent DISE with synchronous tensor palatini electromyograms (TP EMG), and polysomnography (ALICE 6). According to the phenotype of collapse pattern at velum level in DISE, the subjects were divided into group 1 (concentric collapse), group 2 (anteroposterior collapse), and group 3 (lateral collapse). Each group consisted of 13, 14, and 9 subjects, respectively, and was observed the electromyographic indexes at awake, sleep onset, during apnea and the third respiratory cycle after apnea. The active and passive upper airway critical closing pressure (Pcrit) of each group were measured at the same time, and the difference of neuromuscular response between different groups was evaluated. RESULTS: In tonic TPEMG, group 1 showed the highest value during awake and sleep onset, while group 2 was the highest during apnea and after apnea. In peak TPEMG, group 1 showed the highest value during awake. Group 2 showed the highest value during other states. In passive Pcrit and D value (difference between passive Pcrit and active Pcrit), group 2 was the highest, while group 1 was the highest in active Pcrit. Difference was statistically significant. CONCLUSIONS: Under different states of awake, sleep onset, apnea and after apnea, the response force of tensor palatini muscle of OSA subjects with different phenotypes under DISE was different. Group 1 showed the highest EMG values only when awake and sleep onset, and it was most prone to collapse. Group 2 had the highest anatomical load (passive Pcrit) and the highest neuromuscular compensatory effect (D value).

Cerebral Critical Closing Pressure in Concomitant Traumatic Brain Injury and Intracranial Hematomas.

The critical closing pressure (CrCP) is the pressure below which the local pial blood pressure is inadequate to prevent blood flow cessation. The cerebral CrCP in concomitant traumatic brain injury (TBI) and intracranial hematomas (TBI + ICH) remains understudied. The aim was to determine the status of the CrCP at сTBI with and without the ICH development. MATERIAL AND METHODS: The results of the treatment of 90 patients with severe to moderate сTBI were studied (male/female - 49:41). The average age was 34.2 ± 14.4 years. Depending on the presence of ICH, patients were divided into two groups. All patients were subjected to transcranial Doppler of the both middle cerebral arteries, and evaluation of mean arterial pressure (MAP). Based on data obtained, the CrCPs were calculated. Significance was preset to p < 0.05. RESULTS: The mean CrCP values in each group appeared to be significantly higher than a referral value (р < 0.05). The mean CrCP values in the perifocal zone of removed hematoma were significantly higher than in TBI patients without ICH (р = 0.015 and р = 0.048, respectively). Analysis of CrCP values in various types of ICH showed no statistically significant differences (р > 0.05). DISCUSSION: The CrCP significantly differs in the groups of TBI patients with and without ICH. The comparability of the groups in respect to the concomitant injury structure proves that the revealed CrCP changes result from the traumatic compression of the brain.

Cerebrovascular Consequences of Elevated Intracranial Pressure After Traumatic Brain Injury.

We compared various descriptors of cerebral hemodynamics in 517 patients with traumatic brain injury (TBI) who had, on average, elevated (>23 mmHg) or normal (<15 mmHg) intracranial pressure (ICP). In a subsample of 193 of those patients, transcranial Doppler ultrasound (TCD) recordings were made. Arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), cerebral autoregulation indices based on TCD (the mean flow index (Mx; the coefficient of correlation between the the cerebral perfusion pressure CPP and flow velocity) and the autoregulation index (ARI)), and the pressure reactivity index (PRx) were compared between groups. We also analyzed the TCD-based cerebral blood flow (CBF) index (diastolic CBFV/mean CBFV), the spectral pulsatility index (sPI), and the critical closing pressure (CrCP). Finally, we also looked at brain tissue oxygenation (cerebral oxygen partial tension (PbtO2)) in 109 patients. The mean cerebral perfusion pressure (CPP) was lower in the group with elevated ICP (p < 0.01), despite a higher mean arterial pressure (MAP) (p < 0.005) and worse autoregulation (as assessed with the Mx, ARI, and PRx indices), greater CrCP, a lower CBF index, and a higher sPI (all with p values of <0.001). Neither the mean CBFV nor PbtO2 reached significant differences between groups. Mortality in the group with elevated ICP was almost three times greater than that in the group with normal ICP (45% versus 17%). Elevated ICP affects cerebral autoregulation. When autoregulation is not working properly, the brain is exposed to ischemic insults whenever CPP falls.

Impacts of a Pressure Challenge on Cerebral Critical Closing Pressure and Effective Cerebral Perfusion Pressure in Patients with Traumatic Brain Injury.

INTRODUCTION: Cerebral critical closing pressure (CrCP) comprises intracranial pressure (ICP) and arteriolar wall tension (WT). It is the arterial blood pressure (ABP) at which small vessels close and circulation stops. We hypothesized that the increase in WT secondary to a systemic hypertensive challenge would lead to an increase in CrCP and that the "effective" cerebral perfusion pressure (CPPeff; calculated as ABP - CrCP) would give more complete information than the "conventional" cerebral perfusion pressure (CPP; calculated as ABP - ICP). OBJECTIVE: This study aimed to compare CrCP, CPP, and CPPeff changes during a hypertensive challenge in patients with a severe traumatic brain injury. PATIENTS AND METHODS: Data on ABP, ICP, and cerebral blood flow velocity, measured by transcranial Doppler ultrasound, were acquired simultaneously for 30 min both basally and during a hypertensive challenge. An impedance-based CrCP model was used. RESULTS: The following values are expressed as median (interquartile range). There were 11 patients, aged 29 (14) years. CPP increased from 73 (17) to 102 (26) mmHg (P ≤ 0.001). ICP did not change. CrCP changed from 23 (11) to 27 (10) mmHg (P ≤ 0.001). WT increased from 7 (5) to 11 (7) mmHg (P ˂ 0.005). CPPeff changed less than CPP. CONCLUSION: The CPP change was greater than the CPPeff change, mainly because CrCP increased simultaneously with the WT increase as a result of the autoregulatory response. CPPeff provides information about the real driving force generating blood movement.

Critical Closing Pressure by Diffuse Correlation Spectroscopy in a Neonatal Piglet Model.

The critical closing pressure (CrCP) of the cerebral vasculature is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. Because the ABP of preterm infants is low and close to the CrCP, there is often no CBF during diastole. Thus, estimation of CrCP may become clinically relevant in preterm neonates. Transcranial Doppler (TCD) ultrasound has been used to estimate CrCP in preterm infants. Diffuse correlation spectroscopy (DCS) is a continuous, noninvasive optical technique that measures microvascular CBF. Our objective was to compare and validate CrCP measured by DCS versus TCD ultrasound. Hemorrhagic shock was induced in 13 neonatal piglets, and CBF was measured continuously by both modalities. CrCP was calculated using a model of cerebrovascular impedance, and CrCP determined by the two modalities showed good correlation by linear regression, median r 2 = 0.8 (interquartile range (IQR) 0.71-0.87), and Bland-Altman analysis showed a median bias of -3.5 (IQR -4.6 to -0.28). This is the first comparison of CrCP determined by DCS versus TCD ultrasound in a neonatal piglet model of hemorrhagic shock. The difference in CrCP between the two modalities may be due to differences in vasomotor tone within the microvasculature of the cerebral arterioles versus the macrovasculature of a major cerebral artery.

[Establishment of the method for measuring upper airway critical closing pressure].

Objective: To establish a noninvasive method for measuring upper airway critical closing pressure (Pcrit), so as to evaluate collapsibility of the upper airway during sleep. Methods: Pcrit was determined through the use of a noninvasive positive/negative pressure (CPAP/CPNP) ventilator(with independent intellectual property rights) during stageⅡ of non-rapid eye movement sleep. For the direct measurement, Pcrit was the pressure below which the upper airway occluded. For the indirect measurement, nasal pressure was plotted against maximum inspiratory flow (Vimax), and linear regression was used to interpolate the pressure (i.e., Pcrit) at which zero flow occurred. Pcrit was attained from 19 subjects without obstructive sleep apnea syndrome(OSAS), and the correlation between direct and indirect measurement methods was analyzed. Results: Directly measured and indirectly measured Pcrit showed no significant difference [(-7.02±2.74 vs (-7.26±2.96) cmH2O, 1 cmH2O=0.098 kPa; t=1.667, P>0.05] and had a highly significant correlation (r=0.986, P=0.000). Bland-Altman analysis revealed that the mean between-method difference was (0.24±0.53) cmH2O, and 95% limits of agreement ranged from -0.80 to 1.27 cmH2O, and all points except one were within limits of agreement. Conclusion: Pcrit derived from the direct and indirect measurement methods does not differ, and both methods could be used for evaluating the upper airway collapsibility.

Assessment of cerebral hemodynamic parameters using pulsatile versus non-pulsatile cerebral blood outflow models.

BACKGROUND: Prior methods evaluating the changes in cerebral arterial blood volume (∆CaBV) assumed that brain blood transport distal to big cerebral arteries can be approximated with a non-pulsatile flow (CFF) model. In this study, a modified ∆CaBV calculation that accounts for pulsatile blood flow forward (PFF) from large cerebral arteries to resistive arterioles was investigated. The aim was to assess cerebral hemodynamic indices estimated by both CFF and PFF models while changing arterial blood carbon dioxide concentration (EtCO2) in healthy volunteers. MATERIALS AND METHODS: Continuous recordings of non-invasive arterial blood pressure (ABP), transcranial Doppler blood flow velocity (CBFVa), and EtCO2 were performed in 53 young volunteers at baseline and during both hypo- and hypercapnia. The time constant of the cerebral arterial bed (τ) and critical closing pressure (CrCP) were estimated using mathematical transformations of the pulse waveforms of ABP and CBFVa, and with both pulsatile and non-pulsatile models of ∆CaBV estimation. Results are presented as median values ± interquartile range. RESULTS: Both CrCP and τ gave significantly lower values with the PFF model when compared with the CFF model (p ≪ 0.001 for both). In comparison to normocapnia, both CrCP and τ determined with the PFF model increased during hypocapnia [CrCPPFF (mm Hg): 5.52 ± 8.78 vs. 14.36 ± 14.47, p = 0.00006; τPFF (ms): 47.4 ± 53.9 vs. 72.8 ± 45.7, p = 0.002] and decreased during hypercapnia [CrCPPFF (mm Hg): 5.52 ± 8.78 vs. 2.36 ± 7.05, p = 0.0001; τPFF (ms): 47.4 ± 53.9 vs. 29.0 ± 31.3, p = 0.0003]. When the CFF model was applied, no changes were found for CrCP during hypercapnia or in τ during hypocapnia. CONCLUSION: Our results suggest that the pulsatile flow forward model better reflects changes in CrCP and in τ induced by controlled alterations in EtCO2.

The meaning of blood pressure.

Measurement of arterial pressure is one of the most basic elements of patient management. Arterial pressure is determined by the volume ejected by the heart into the arteries, the elastance of the walls of the arteries, and the rate at which the blood flows out of the arteries. This review will discuss the three forces that determine the pressure in a vessel: elastic, kinetic, and gravitational energy. Emphasis will be placed on the importance of the distribution of arterial resistances, the elastance of the walls of the large vessels, and critical closing pressures in small arteries and arterioles. Regulation of arterial pressure occurs through changes in cardiac output and changes in vascular resistance, but these two controlled variables can sometimes be in conflict.

Critical Closing Pressure During a Controlled Increase in Intracranial Pressure.

OBJECTIVES: The objectives were to compare three methods of estimating critical closing pressure (CrCP) in a scenario of a controlled increase in intracranial pressure (ICP) induced during an infusion test in patients with suspected normal pressure hydrocephalus (NPH). METHODS: We retrospectively analyzed data from 37 NPH patients who underwent infusion tests. Computer recordings of directly measured intracranial pressure (ICP), arterial blood pressure (ABP) and transcranial Doppler cerebral blood flow velocity (CBFV) were used. The CrCP was calculated using three methods: first harmonics ratio of the pulse waveforms of ABP and CBFV (CrCPA) and two methods based on a model of cerebrovascular impedance, as a function of cerebral perfusion pressure (CrCPinv), and as a function of ABP (CrCPninv). RESULTS: There is good agreement among the three methods of CrCP calculation, with correlation coefficients being greater than 0.8 (p < 0.0001). For the CrCPA method, negative values were found for about 20% of all results. Negative values of CrCP were not observed in estimators based on cerebrovascular impedance. During the controlled rise of ICP, all three estimators of CrCP increased significantly (p < 0.05). The strongest correlation between ICP and CrCP was found for CrCPinv (median R = 0.41). CONCLUSION: Invasive CrCP is most sensitive to variations in ICP and can be used as an indicator of the status of the cerebrovascular system during infusion tests.

Effect of Mild Hypocapnia on Critical Closing Pressure and Other Mechanoelastic Parameters of the Cerebrospinal System.

OBJECTIVE: Brain arterial critical closing pressure (CrCP) has been studied in several diseases such as traumatic brain injury (TBI), subarachnoid haemorrhage, hydrocephalus, and in various physiological scenarios: intracranial hypertension, decreased cerebral perfusion pressure, hypercapnia, etc. Little or nothing so far has been demonstrated to characterise change in CrCP during mild hypocapnia. METHOD: We retrospectively analysed recordings of intracranial pressure (ICP), arterial blood pressure (ABP) and blood flow velocity from 27 severe TBI patients (mean 39.5 ± 3.4 years, 6 women) in whom a ventilation increase (20% increase in respiratory minute volume) was performed over 50 min as part of a standard clinical CO2 reactivity test. CrCP was calculated using the Windkessel model of cerebral arterial flow. Arteriolar wall tension (WT) was calculated as a difference between CrCP and ICP. The compartmental compliances arterial (C a ) and cerebrospinal fluid space (C i ) were also evaluated. RESULTS: During hypocapnia, ICP decreased from 17±6.8 to 13.2±6.6 mmHg (p < 0.000001). Wall tension increased from 14.5 ± 9.9 to 21.7±9.1 mmHg (p < 0.0002). CrCP, being a sum of WT + ICP, changed significantly from 31.5 ± 11.9 mmHg to 34.9±11.1 mmHg (p < 0.002), and the closing margin (ABP-CrCP) remained constant at an average value of 60 mmHg. C a decreased significantly during hypocapnia by 30% (p < 0.00001) and C i increased by 26% (p < 0.003). CONCLUSION: During hypocapnia in TBI patients, ICP decreases and WT increases. CrCP increases slightly as the rise in wall tension outweighs the decrease in ICP. The closing margin remained unchanged, suggesting that the risk of hypocapnia-induced ischemia might not be increased.

The cerebrocardiovascular response to periodic squat-stand maneuvers in healthy subjects: a time-domain analysis.

Squat-stand maneuvers (SSMs) have been used to improve the coherence of transfer function analysis (TFA) estimates during the assessment of dynamic cerebral autoregulation (dCA). There is a need to understand the influence of peripheral changes resulting from SSMs on cerebral blood flow, which might confound estimates of dCA. Healthy subjects ( n = 29) underwent recordings at rest (5-min standing) and 15 SSMs (0.05 Hz). Heart rate (three-lead ECG), end-tidal CO2 (capnography), blood pressure (Finometer), cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery), and the angle of the thigh (tilt sensor) were measured continuously. The response of CBV to SSMs was decomposed into the relative contributions of mean arterial pressure (MAP), resistance-area product (RAP), and critical closing pressure (CrCP). Upon squatting, a rise in MAP (83.6 ± 21.1% contribution) was followed by increased CBV. A dCA response could be detected, determined by adjustments in RAP and CrCP (left hemisphere) with peak contributions of 24.8 ± 12.7% and 27.4 ± 22.8%, respectively, at different times during SSMs. No interhemispheric differences were detected. During standing, the contributions of MAP, RAP, and CrCP changed considerably. In conclusion, the changes of CBV subcomponents during repeated SSMs indicate a complex response of CBV to SSMs that can only be partially explained by myogenic mechanisms. More work is needed to clarify the potential contribution of other cofactors, such as breath-to-breath changes in Pco2, heart rate, stroke volume, and the neurogenic component of dCA. NEW & NOTEWORTHY Here, we describe the different contributions to the cerebral blood flow response after squat-stand maneuvers. Furthermore, we demonstrate the complex interaction of peripheral and cerebral parameters for the first time. Moreover, we show that the cerebral blood velocity response to squatting is likely to include a significant metabolic component.

Upper airway stabilization by osteopathic manipulation of the sphenopalatine ganglion versus sham manipulation in OSAS patients: a proof-of-concept, randomized, crossover, double-blind, controlled study.

BACKGROUND: Osteopathic manipulative treatment (OMT) of the sphenopalatine ganglion (SPG) is used empirically for the treatment of rhinitis and snoring and is thought to increase pharyngeal stability. This trial was designed to study the effects of this treatment on pharyngeal stability evaluated by critical closing pressure in obstructive sleep apnoea syndrome. METHODS: This single-centre, randomized, crossover, double-blind study compared active manipulation and sham manipulation of the SPG. Randomization was computer-generated. Patients each received one active manipulation and one sham manipulation at an interval of 21 days and were evaluated 30 min and 48 h after each session administered by a qualified osteopath. Neither the patients, nor the investigator performing the evaluations were informed about the order of the two techniques (double-blind). The primary endpoint was the percentage of responding patients presenting increased pharyngeal stability defined by a variation of critical closing pressure (Pcrit) of at least -4 cmH2O at 30 min. Secondary endpoints were the variation of Pcrit in absolute values, sleepiness and snoring. Others endpoints were lacrimation (Schirmer's test), induced pain, sensations experienced during OMT. RESULTS: Ten patients were included and nine (57 [50; 58] years, comprising 7 men, with an apnoea-hypopnoea index of 31.0 [25.5; 33.2]/h; (values are median [quartiles])) were analysed. Seven patients were analysed for the primary endpoint and nine patients were analysed for secondary endpoints. Five patients responded after active manipulation versus no patients after sham manipulation (p = 0.0209). Active manipulation induced more intense pain (p = 0.0089), increased lacrimation (ns) and more tactile, nociceptive and gustatory sensations (13 versus 1) compared to sham manipulation. No significant difference was observed for the other endpoints. CONCLUSIONS: Osteopathic manipulative treatment of the SPG may improve pharyngeal stability in obstructive sleep apnoea syndrome. This trial validates the feasibility of the randomized, controlled, double-blind methodology for evaluation of this osteopathic treatment. Studies on a larger sample size must specify the efficacy on the apnoea-hypopnoea index. TRIAL REGISTRATION: The study was retrospectively registered in the clinicaltrial.gov registry under reference NCT01193738 on 1st September 2010 (first inclusion May 19, 2010).

Elevated Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants.

OBJECTIVE: To determine whether the diastolic closing margin (DCM), defined as diastolic blood pressure minus critical closing pressure, is associated with the development of early severe intraventricular hemorrhage (IVH). STUDY DESIGN: A reanalysis of prospectively collected data was conducted. Premature infants (gestational age 23-31 weeks) receiving mechanical ventilation (n = 185) had ∼1-hour continuous recordings of umbilical arterial blood pressure, middle cerebral artery cerebral blood flow velocity, and PaCO2 during the first week of life. Models using multivariate generalized linear regression and purposeful selection were used to determine associations with severe IVH. RESULTS: Severe IVH (grades 3-4) was observed in 14.6% of the infants. Irrespective of the model used, Apgar score at 5 minutes and DCM were significantly associated with severe IVH. A clinically relevant 5-mm Hg increase in DCM was associated with a 1.83- to 1.89-fold increased odds of developing severe IVH. CONCLUSION: Elevated DCM was associated with severe IVH, consistent with previous animal data showing that IVH is associated with hyperperfusion. Measurement of DCM may be more useful than blood pressure in defining cerebral perfusion in premature infants.

Cerebral Critical Closing Pressure During Infusion Tests.

We studied possible correlations between cerebral hemodynamic indices based on critical closing pressure (CrCP) and cerebrospinal fluid (CSF) compensatory dynamics, as assessed during lumbar infusion tests. Our data consisted of 34 patients with normal-pressure hydrocephalus who undertook an infusion test, in conjunction with simultaneous transcranial Doppler ultrasonography (TCD) monitoring of blood flow velocity (FV). CrCP was calculated from the monitored signals of ICP, arterial blood pressure (ABP), and FV, whereas vascular wall tension (WT) was estimated as CrCP - ICP. The closing margin (CM) expresses the difference between ABP and CrCP. ICP increased during infusion from 6.67 ± 4.61 to 24.98 ± 10.49 mmHg (mean ± SD; p < 0.001), resulting in CrCP rising by 22.93 % (p < 0.001), with WT decreasing by 11.33 % (p = 0.005) owing to vasodilatation. CM showed a tendency to decrease, albeit not significantly (p = 0.070), because of rising ABP (9.12 %; p = 0.005), and was significantly different from zero for the whole duration of the tests (52.78 ± 22.82 mmHg; p < 0.001). CM at baseline correlated inversely with brain elasticity (R = -0.358; p = 0.038). Neither CrCP nor WT correlated with CSF compensatory parameters. Overall, CrCP increases and WT decreases during infusion tests, whereas CM at baseline pressure may act as a characterizing indicator of the cerebrospinal compensatory reserve.

The Ontogeny of Cerebrovascular Critical Closing Pressure.

Premature infants are at risk of vascular neurological insults. Hypotension and hypertension are considered injurious, but neither condition is defined with consensus. Critical closing pressure (CrCP) is the arterial blood pressure (ABP) at which cerebral blood flow ceases. CrCP may serve to define subject-specific low or high ABP. Our objective was to quantify CrCP as a function of gestational age (GA). One hundred eighty-six premature infants with a GA range of 23-33 weeks, were monitored with umbilical artery catheters and transcranial Doppler insonation of middle cerebral artery flow velocity (FV) for 1-h sessions over the first week of life. CrCP was calculated using an impedance model derivation with Doppler-based estimations of cerebrovascular resistance and compliance. CrCP increased significantly with GA (r = 0.47; slope = 1.4 mmHg/week gestation), an association that persisted with multivariate analysis (p < 0.001). Higher diastolic ABP and higher GA were associated with increased CrCP (p <0.001 for both). CrCP increases significantly at the end of the second and beginning of the third trimester. The low CrCP observed in premature infants may explain their ability to tolerate low ABP without global cerebral infarct or hemorrhage.

The Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants.

Premature infants are at an increased risk of intraventricular hemorrhage (IVH). The roles of hypotension and hyperemia are still debated. Critical closing pressure (CrCP) is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. When diastolic ABP is equal to CrCP, CBF occurs only during systole. The difference between diastolic ABP and CrCP is the diastolic closing margin (DCM). We hypothesized that a low DCM was associated with IVH. One hundred eighty-six premature infants, with a gestational age (GA) range of 23-33 weeks, were monitored with umbilical artery catheters and transcranial Doppler insonation of middle cerebral artery flow velocity for 1-h sessions over the first week of life. CrCP was calculated linearly and using an impedance model. A multivariate generalized linear regression model was used to determine associations with severe IVH (grades 3-4). An elevated DCM by either method was associated with IVH (p < 0.0001 for the linear method; p < 0.001 for the impedance model). Lower 5-min Apgar scores, elevated mean CBF velocity, and lower mean ABP were also associated with IVH (p < 0.0001). Elevated DCM, not low DCM, was associated with severe IVH in this cohort.