Search

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (V(T)). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients. OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference. DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries. MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as V(T) of 8 ml kg(−1) or less predicted bodyweight (PBW). A V(T) was deemed ‘default’ if the set V(T) was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation. RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default V(T) was often set, both in women and men; mode V(T) was 500 ml. Median [IQR] V(T) was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg(−1) PBW, P*** < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P*** < 0.001]. In the mediation analysis, patients’ height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default V(T). CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher V(T) than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Hemodynamic instability associated with acute renal replacement therapy (aRRT, HIRRT) and/or with acute kidney injury (AKI) is frequently observed in the intensive care unit; it affects patients’ renal recovery, and negatively impacts short- and long-term mortality. A thorough understanding of mechanisms underlying HIRRT and AKI-related hemodynamic instability may allow the physician in adopting adequate strategies to prevent their occurrence and reduce their negative consequences. The aim of this review is to summarize the main alterations occurring in patients with AKI and/or requiring aRRT of those homeostatic mechanisms which regulate hemodynamics and oxygen delivery. In particular, a pathophysiological approach has been used to describe the maladaptive interactions between cardiac output and systemic vascular resistance occurring in these patients and leading to hemodynamic instability. Finally, the potential positive effects of aRRT on these pathophysiological mechanisms and on restoring hemodynamic stability have been described.

Background: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. Methods: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. Results: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. Conclusion: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely.

Death from the novel coronavirus disease (COVID-19) predominantly occurs by refractory hypoxemia [1]. Some Authors have suggested that this type of respiratory failure differs from typical Acute Respiratory Distress Syndrome (ARDS) [2]. Patients with COVID-19 can present with (i) higher respiratory system compliance, and (ii) lower amount of non-ventilated lung tissue than expected given the severity of hypoxemia. These two elements may suggest a different primary cause of gas exchange impairment in COVID-19 compared to ARDS of another origin: excessive perfusion of small non-normally ventilated lung regions rather than a large anatomical shunt [3]. In line with this model, a recent series has revealed the presence of diffuse pulmonary endothelial injury and microthrombosis in COVID-19 lung pathology [4]. Given the novelty of COVID-19, its treatment is currently grounded on our knowledge of ARDS. Modern supportive therapy of ARDS generally consists of endotracheal intubation and mechanical ventilation with supplemental oxygen and Positive End Expiratory Pressure (PEEP), along with muscle paralysis, prone positioning, and ExtraCorporeal Membrane Oxygenation (ECMO) for the most severe cases [5,6]. Inhaled nitric oxide (iNO) can be considered as rescue therapy for hypoxemia due to its potent vasodilator effect on the pulmonary circulation [7]. International guidelines [5], and experts in the field [6,[8], [9], [10]], all suggest considering iNO even for refractory hypoxemia due to COVID-19. However, there are no strong clinical data to support this indication. Herein we describe the response to iNO in a small group of mechanically ventilated patients with severe COVID admitted to our Intensive Care Unit.

The benefit of induced hyperventilation for intracranial pressure (ICP) control after severe traumatic brain injury (TBI) is controversial. In this study, we investigated the impact of early and sustained hyperventilation on compliances of the cerebral arteries and of the cerebrospinal (CSF) compartment during mild hyperventilation in severe TBI patients. We included 27 severe TBI patients (mean 39.5 ± 3.4 years, 6 women) in whom an increase in ventilation (20% increase in respiratory minute volume) was performed during 50 min as part of a standard clinical CO(2) reactivity test. Using a new mathematical model, cerebral arterial compliance (Ca) and CSF compartment compliance (Ci) were calculated based on the analysis of ICP, arterial blood pressure, and cerebral blood flow velocity waveforms. Hyperventilation initially induced a reduction in ICP (17.5 ± 6.6 vs. 13.9 ± 6.2 mmHg; p < 0.001), which correlated with an increase in Ci (r(2) = 0.213; p = 0.015). Concomitantly, the reduction in cerebral blood flow velocities (CBFV, 74.6 ± 27.0 vs. 62.9 ± 22.9 cm/sec; p < 0.001) marginally correlated with the reduction in Ca (r(2) = 0.209; p = 0.017). During sustained hyperventilation, ICP increased (13.9 ± 6.2 vs. 15.3 ± 6.4 mmHg; p < 0.001), which correlated with a reduction in Ci (r(2) = 0.297; p = 0.003), but no significant changes in Ca were found during that period. The early reduction in Ca persisted irrespective of the duration of hyperventilation, which may contribute to the lack of clinical benefit of hyperventilation after TBI. Further studies are needed to determine whether monitoring of arterial and CSF compartment compliances may detect and prevent an adverse ischemic event during hyperventilation.

BACKGROUND Changes in partial pressure of carbon dioxide (PaCO2) are associated with a decrease in cerebral blood flow (CBF) during hypocapnia and an increase in CBF during hypercapnia. However, the effects of changes in PaCO2 on cerebral arterial compliance (Ca) are unknown. METHODS We assessed the changes in Ca in 20 normal subjects using monitoring of arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). Cerebral arterial blood volume (CaBV) was extracted from CBFV. Ca was defined as the ratio between the pulse amplitudes of CaBV (AMPCaBV) and ABP (AMPABP). All parameters were recorded during normo-, hyper-, and hypocapnia. RESULTS During hypocapnia, Ca was significantly lower than during normocapnia (.10 ± .04 vs. .17 ± .06; P < .001) secondary to a decrease in AMPCaBV (1.3 ± .4 vs. 1.9 ± .5; P < .001) and a concomitant increase in AMPABP (13.8 ± 3.4 vs. 11.6 ± 1.7 mmHg; P < .001). During hypercapnia, there was no change in Ca compared with normocapnia. Ca was inversely correlated with the cerebrovascular resistance during hypo- (R2= 0.86; P < .001), and hypercapnia (R2= 0.61; P < .001). CONCLUSION Using a new mathematical model, we have described a reduction of Ca during hypocapnia. Further studies are needed to determine whether Ca may be an independent predictor of outcome in pathological conditions.

Background: A decrease in arterial compliance of the internal carotid artery has been associated with an increased risk in ipsilateral ischaemic stroke. However, so far, no technique has been validated to monitor the compliance of intracerebral arteries (Ca) in patients with carotid artery disease. In this study, we sought to monitor Ca in patients with unilateral symptomatic disease and to determine its variations during changes in PaCO2. Methods: We studied 18 patients with unilateral symptomatic internal carotid artery stenosis >50% or occlusion. Patients underwent monitoring of arterial blood pressure (ABP) and middle cerebral artery cerebral blood flow velocities (CBFV) during baseline, hyperventilation and 5%CO2 inhalation. Ca was calculated from pulsatile amplitudes of ABP and Cerebral arterial blood volume, extracted from the CBFV waveform using a new mathematical model. Results: At baseline, the decrease in Ca on the diseased side was correlated with the degree of stenosis (r = −0.35; P = 0.01). During hypocapnia, Ca was lower compared to baseline on the normal side (P = 0.004) and on the diseased side (P = 0.04). Ca reactivity, reflecting the changes in Ca per changes in 1 mmHg PaCO2, was lower on the diseased side between baseline and hypocapnia (3.4 vs. 2.6%; P = 0.04). During hypercapnia, no changes in Ca on the diseased (P = 0.8) nor on the normal sides (P = 0.2) were observed. Conclusions: The decrease in cerebral arterial compliance the side of stenosis/occlusion was correlated with the severity of the internal carotid artery disease. Further studies are needed to determine whether Ca may improve the prediction of ischaemic events in symptomatic and asymptomatic patients.

Increased slow-wave activity in intracranial pressure (ICP) signifies an exhausted cerebrospinal compensatory reserve across a range of conditions. In this study, we attempted to describe synchronisation between slow waves of ICP and of near-infrared spectroscopy (NIRS) variables during controlled elevation of ICP. Nineteen patients presenting with symptomatic hydrocephalus underwent a Computerised Infusion Test. NIRS-derived indices, ICP and arterial blood pressure (ABP) were recorded simultaneously. ICP increased from 9.3 (6.0) mmHg to a 17.1 (8.9) mmHg during infusion. Slow waves in ICP were accompanied by concurrent waves in each NIRS variable (including deoxygenated haemoglobin (Hb) and oxygenated haemoglobin (HbO2)) with a mean coherence of >0.7 and no significant phase shift. In the same bandwidth (0.3–1.8 min−1), ABP fluctuations occurred with a coherence of 0.77 and phase lead of 40° with respect to ICP. The power of ICP slow waves increased significantly during infusion plateau with a corresponding increase in power of Hb waves. Slow fluctuations in cerebral oximetry as detected by NIRS coincide with and are implicated in the origin of ICP slow waves and increases during periods of exhausted cerebrospinal compensatory reserve. NIRS may be used as a non-invasive marker of increased ICP slow waves (and therefore reduced CSF compensatory reserve).

Background: During the last decade, with the development of on-line monitoring and waveform analysis, inte- gration of brain signals has increasingly been used in patients with traumatic brain injury (TBI) to guide clinical manage- ment and predict outcome. Objective: The goal of this review is to describe current methodology for brain signal integration in TBI patients focusing on 'reactivity indices'. Methods: We reviewed selected techniques to monitor patients in the acute phase of TBI using the comparison and inte- gration of different physiological signals. The autoregulation indices, Mx and Mxa were defined as the moving correla- tion between cerebral blood flow velocities (CBFV) and cerebral perfusion pressure (CPP) or arterial blood pressure (ABP), respectively. The cerebrovascular pressure reactivity index PRx was defined as the moving correlation coefficient between ABP and intracranial pressure (ICP). The oxygen reactivity index, Orx, was defined as the moving correlation co- efficient between brain tissue oxygenation and CPP. Finally, Tox was defined as the moving correlation coefficient be- tween brain tissue oxygenation measured by Near Infrared Spectroscopy (NIRS) and ABP. Results: Both Mx > 0.3 and Mxa > 0.45 as well as an asymmetry of Mx between both hemispheres of the brain in the acute phase were associated with poor outcome. PRx may be used to determine the individual optimal CPP and is also a powerful and independent predictor of outcome. Orx showed conflicting results and more studies are need to determine its role in the acute setting of TBI. Studies concerning the role of NIRS in the acute phase of TBI are ongoing. Conclusion: Multimodal neuromonitoring (MNM) is useful in the neuroICU as it provides valuable insights into the pathophysiological mechanisms occurring in the acute phase of TBI. Furthermore, indices obtained with MNM have been shown to be strong predictors of outcome. Further studies combining current and emergent techniques such as NIRS em- phasize on the ability for MNM to continuously evolve.

We compared autoregulation monitored with cortical laser Doppler flowmetry (LDF) and autoregulation monitored with transcranial Doppler (TCD) in the middle cerebral artery (MCA) to verify the hypothesis that, following brain trauma, cortical vessel autoregulation to intracranial hypertension is different than assessed in the MCA.Data collected from 29 head injured patients were analysed retrospectively. Arterial blood pressure (ABP), intracranial pressure (ICP), flow velocity (FV) of the MCA and cortical flux (LDF) were monitored. Indices of cortical autoregulation (Lx) and autoregulation of cerebral blood flow in the MCA (Mx) were calculated as a moving correlation coefficient between slow waves of LDF and cerebral perfusion pressure (CPP) (Lx) or FV and CPP (Mx), respectively. Intact autoregulation was indicated by negative values for Lx and Mx; disturbed autoregulation was reflected by positive values.FV and LDF showed a high coherence in the slow wave spectrum of 1-4 cycles/min (mean: 0.79 +/- 0.12), indicating that similar information regarding autoregulation is carried by both signals. Mx and Lx correlated in all patients (R=0.43, p=0.02). On average, Lx was significantly higher than Mx; the mean difference was 0.13 +/- 0.38 (p=0.032), potentially due to severe intracranial hypertension above 40 mmHg, driving CPP values below 60 mmHg.After traumatic brain injury, cortical autoregulation appears to be worse than autoregulation assessed in the MCA during rising ICP and falling CPP. When CPP is above 60 mmHg, cortical assessed autoregulation is similar to autoregulation assessed in the MCA.

We aimed to study synchronisation between ICP and near infrared spectroscopy (NIRS) variables induced by vasogenic waves of ICP during an infusion study in hydrocephalic patients and after TBI. Nineteen patients presenting with hydrocephalus underwent a diagnostic intraventricular constant-flow infusion test. The original concept of the methodology, presented in the current paper, was derived from this material. Then the method was applied in 40 TBI patients, with results reported in an observational manner. During monitoring, NIRS deoxygenated and oxygenated haemoglobin (Hb, HbO(2)) were recorded simultaneously with ICP. Moving correlation coefficient (6 min) between Hb and HbO(2) was tested as a marker of the slow vasogenic waves of ICP.During infusion studies ICP increased from 10.7 (5.1) mmHg to a plateau of 18.9 (7.6) mmHg, which was associated with an increase in the power of slow ICP waves (p = 0.000017). Fluctuations of Hb and HbO(2) at baseline negatively correlated with each other, but switched to high positive values during periods of increased ICP slow-wave activity during infusion (p0.001). Similar behaviour was observed in TBI patients: baseline negative Hb/HbO(2) correlation changed to positive values during peaks of ICP of vasogenic nature.Correlating changes in Hb and HbO(2) may be of use as a method of non-invasive detection of vasogenic ICP waves.

We aimed to study synchronisation between ICP and near infrared spectroscopy (NIRS) variables induced by vasogenic waves of ICP during an infusion study in hydrocephalic patients and after TBI. Nineteen patients presenting with hydrocephalus underwent a diagnostic intraventricular constant-flow infusion test. The original concept of the methodology, presented in the current paper, was derived from this material. Then the method was applied in 40 TBI patients, with results reported in an observational manner. During monitoring, NIRS deoxygenated and oxygenated haemoglobin (Hb, HbO2) were recorded simultaneously with ICP. Moving correlation coefficient (6 min) between Hb and HbO2 was tested as a marker of the slow vasogenic waves of ICP.

Strong correlation between mean intracranial pressure (ICP) and its pulse wave amplitude (AMP) has been demonstrated in different clinical scenarios. We investigated the relationship between invasive mean arterial blood pressure (ABP) and AMP to explore its potential role as a descriptor of cerebrovascular pressure reactivity after traumatic brain injury (TBI). We retrospectively analyzed data of patients suffering from TBI with brain monitoring. Transcranial Doppler blood flow velocity, ABP, ICP were recorded digitally. Cerebral perfusion pressure (CPP) and AMP were derived. A new index—pressure-amplitude index (PAx)—was calculated as the Pearson correlation between (averaged over 10 s intervals) ABP and AMP with a 5 min long moving average window. The previously introduced transcranial Doppler-based autoregulation index Mx was evaluated in a similar way, as the moving correlation between blood flow velocity and CPP. The clinical outcome was assessed after 6 months using the Glasgow outcome score. 293 patients were studied. The mean PAx was −0.09 (standard deviation 0.21). This negative value indicates that, on average, an increase in ABP causes a decrease in AMP and vice versa. PAx correlated strong with Mx (R 2 = 0.46, P

Background and Purpose— In patients with subarachnoid hemorrhage, the assessment of cerebral autoregulation aids in prognosis as well as detection of vasospasm. Mx is a validated index of cerebral autoregulation based on measures of cerebral perfusion pressure and mean flow velocity on transcranial Doppler but is impractical for longer-term monitoring. Near-infrared spectroscopy is noninvasive and suitable for continuous monitoring of cerebral tissue oxygenation using the Tissue Oxygenation Index. In this study, we compared near-infrared spectroscopy-based indices of cerebral autoregulation (TOx) with Mx in patients with subarachnoid hemorrhage. Methods— Arterial blood pressure, intracranial pressure, mean flow velocity, and Tissue Oxygenation Index were recorded. Mx and TOx were calculated as moving correlation coefficients between 10-second averaged values of cerebral perfusion pressure and mean flow velocity and between cerebral perfusion pressure and Tissue Oxygenation Index. We also calculated TOxA, the moving correlation coefficient between arterial blood pressure and Tissue Oxygenation Index. Results— Fifty-one recording sessions were performed in 27 patients with subarachnoid hemorrhage with a total duration of 62.5 hours. Correlations of Mx and TOx over time varied markedly among individual recordings. However, time-averaging over the entire recording interval in each of the 51 recordings, we found correlations between Mx and TOx and between Mx and TOxA were highly significant. This correlation was even stronger after correction for multiple sampling for each patient, reaching r =0.81 for Mx and TOx and r =0.72 for Mx and TOxA. Conclusion— Near-infrared spectroscopy can be used to continuously assess cerebral autoregulation in adults after subarachnoid hemorrhage.

Monitoring of cerebrovascular pressure reactivity (PRx) has diagnostic and prognostic value in head-injured patients, but requires invasive monitoring of intracranial pressure (ICP). Near infrared spectroscopy (NIRS) is a noninvasive method that is suitable for continuous detection of cerebral blood volume changes. We compared a NIRS-based index of cerebrovascular reactivity, called total hemoglobin reactivity (THx), against standard measurements of PRx in a prospective observational study. Forty patients with closed-head injury were monitored daily with arterial blood pressure (ABP), ICP, and a NIRS-based total hemoglobin index. PRx and THx were calculated as the moving correlation coefficients using 5-min time windows between 10-sec averaged values of ICP and ABP, and total hemoglobin index and ABP, respectively. A total of 120 recordings were performed between the median first (IQR 0.75-2) and fourth (IQR 2-6) day after head injury, giving a total duration of 1760 hours. PRx and THx demonstrated a significant association across averaged individual recordings (r = 0.49, p < 0.0001), and across patients (r = 0.56, p = 0.0002). Assessment of optimal cerebral perfusion pressure (CPP) and ABP using THx was possible in about 50% of recordings, and showed a significant agreement with the optimal CPP and ABP assessed with PRx. THx may be of diagnostic value to optimize therapy oriented toward restoration and continuity of cerebrovascular reactivity, especially in patients for whom direct ICP monitoring is not feasible.

The pulsatile component of intracranial pressure (ICP) has been shown to be a predictor of outcome in normal pressure hydrocephalus (NPH) and traumatic brain injury (TBI). Experimental studies have demonstrated that the pulse amplitude of ICP (AMP(ICP)) is dependent on the mean ICP (mICP), and on the pulse amplitude of the cerebral arterial blood volume (AMP(CaBV)), according to the exponential craniospinal compliance curve. In this study, we compared the influence of mICP and AMP(CaBV) on AMP(ICP) in patients with NPH (infusion study) and TBI (spontaneous recording). We retrospectively analyzed 25 NPH and 43 TBI patients with continuous monitoring of ICP and cerebral blood flow velocity (CBFV), as assessed with transcranial doppler. AMP(CaBV) was extracted from the CBFV waveform. The influence of mICP and AMP(CaBV) on AMP(ICP) were determined using partial coefficients a, b, and c of the multiple regression model: AMP(ICP) = a * mICP + b * AMP(CaBV) + c. AMP(ICP) was more dependent on mICP in NPH patients than in TBI patients (partial coefficient a = 0.93 versus -0.03; p < 0.001). On the contrary, AMP(ICP) was more dependent on AMP(CaBV) in patients with TBI than in those with NPH (b = 0.86 versus 0.10; p < 0.001). This study shows that AMP(ICP) depends mostly on changes in mean ICP during cerebrospinal fluid (CSF) infusion studies in patients with NPH, and on changes in cerebral arterial blood volume (AMP(CaBV)) in TBI patients. Further clinical studies will reveal whether AMP(ICP) is a better indicator of clinical severity and outcome than mICP in TBI and NPH patients.

Plateau waves often develop in neurointensive care patients. They are sudden increases in intracranial pressure (ICP) that lead to dramatic decreases of cerebral perfusion pressure (CPP) and can therefore contribute to ischemic secondary brain insult. The aim of this study was to analyze the occurrence of plateau waves in head injured patients requiring neurocritical care, their relation with cerebral autoregulation and impact on outcome. Data were analyzed retrospectively in 444 head injured patients admitted to Neuroscience Critical Care Unit of Addenbrooke’s Hospital in Cambridge, UK. Arterial blood pressure (ABP), intracranial pressure (ICP), heart rate (HR) were digitally recorded and derived indices calculated. Primary monitoring data, autoregulation indices, outcome of patients, initial CT findings (in a subgroup of patients), brain tissue monitoring data (in a subgroup) were compared between patients who developed plateau waves and those who did not. Plateau waves were observed in 109/444 patients (24.5%). They were significantly more frequent in younger patients. Impaired cerebrovascular pressure reactivity and depleted compensatory reserve were associated with vasodilatation on the top of the wave. Plateau waves were not associated with poorer outcome unless the episodes lasted for a long time (longer than 30–40 min). Plateau waves were more frequently seen in patients with lesser midline shift, lower volume of contusion on CT scan, absence of skull fractures, and lower brain tissue concentration of carbon dioxide. Plateau waves are frequent phenomenon. They are not associated with worse outcome unless they lead to sustained intracranial hypertension.

The study aimed to develop a computational method for assessing relative changes in compartmental compliances within the brain: the arterial bed and the cerebrospinal space. The method utilizes the relationship between pulsatile components in the arterial blood volume, arterial blood pressure (ABP) and intracranial pressure (ICP). It was verified by using clinical recordings of intracranial pressure plateau waves, when massive vasodilatation accompanying plateau waves produces changes in brain compliances of the arterial bed (C(a)) and compliance of the cerebrospinal space (C(i)). Ten patients admitted after head injury with a median Glasgow Coma Score of 6 were studied retrospectively. ABP was directly monitored from the radial artery. Changes in the cerebral arterial blood volume were assessed using Transcranial Doppler (TCD) ultrasonography by digital integration of inflow blood velocity. During plateau waves, ICP increased (P = 0.001), CPP decreased (P = 0.001), ABP remained constant (P = 0.532), blood flow velocity decreased (P = 0.001). Calculated compliance of the arterial bed C(a) increased significantly (P = 0.001); compliance of the CSF space C(i) decreased (P = 0.001). We concluded that the method allows for continuous monitoring of relative changes in brain compartmental compliances. Plateau waves affect the balance between vascular and CSF compartments, which is reflected by the inverse change of compliance of the cerebral arterial bed and global compliance of the CSF space.

Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) may develop during anticoagulant treatment in patients submitted to various regimens of unfractionated or low-molecular weight heparins. Several molecules have been studied as alternative anticoagulants in patients with HIT or HITT, including danaparoid, argatroban, lepirudin. Lepirudin requires dosage adjustments in patients with renal insufficiency and has potential for antibody formation. Argatroban requires dosage adjustments in patients with hepatic insufficiency. Argatroban increases the International Normalized Ratio (INR) when co-administered with warfarin, leading to dosage difficulties when transitioning to warfarin therapy. Anticoagulation of patients with HIT or HITT may be limited by antibodies cross-reactivity with danaparoid and by new generation of antibodies with lepirudin. Fondaparinux is the first of a new class of synthetic antithrombotics: the selective inhibitors of coagulation factor Xa. It is the most advanced competitor of low molecular weight heparins, which are the reference drugs in prophylaxis and treatment of venous thromboembolism. Fondaparinux does not bind to platelet factor 4 (PF4) and does not react with anti-PF4/heparin antibodies in in vitro testing. We treated 20 patients who develop HIT (3 patients) or HITT (17 patients, of whom 4 had both DVT and PE). Nine patients were previously submitted to extracorporeal circulation with unfractionated heparin (UFH) followed by low-molecular weight heparin (LMWH) for major cardiac surgery. The remaining patients had been previously treated with either UHF or LMWH at therapeutic or prophylactic dosage in internal medicine or surgery wards. In the 17 patients who developed HITT, we applied therapeutic dosages of fondaparinux, i.e. 7.5 mg QD or lower, accordingly with their bleeding risk. To the remaining patients with HIT we gave prophylactic dosages of fondaparinux, i.e. 2.5 mg QD. Patients with HITT were treated for 4 to 25 days before starting warfarin. Fondaparinux was stopped when INR of 2.0 or more was reached. All patients showed a significant reduction of their thromboembolic burden. One episode of major bleeding was recorded in a post-surgical patient. All patients but one showed sustained normalization of the platelet number. In the remaining patient platelet count remained unchanged. Treatment was switched from fondaparinux to lepirudin and after few days her platelets reverted to close-to-normal levels. In seven patients, submitted to therapeutic dosages of fondaparinux, anti-PF4/heparin antibody titers were determined using a PF4/heparin enzyme-linked immunosorbent assay (ELISA): in all cases antibody levels progressively decreased close to disappearance by 30–45 days. This series of cases provides further evidence for the safety and efficacy of fondaparinux in the treatment of both HIT or HITT.