Towards optimization of ceftazidime dosing in obese ICU patients: the end of the 'one-size-fits-all' approach?

BACKGROUND: Ceftazidime is commonly used as a key antibiotic against Pseudomonas aeruginosa in critically ill patients. ICU patients have severely altered and variable antibiotic pharmacokinetics, resulting in lower antimicrobial concentrations and potentially poor outcome. Several factors, including obesity and renal function, may influence pharmacokinetics. Thus, the objective of the study was to evaluate the impact of obesity and renal function on ceftazidime plasma concentrations and dosing regimen in ICU patients. METHODS: All consecutive adult patients from six ICUs, treated with continuous ceftazidime infusion and under therapeutic drug monitoring evaluation, were included. Obesity was defined as BMI ≥30 kg/m². Glomerular filtration rate (GFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration formula. The ceftazidime recommended target for plasma concentrations was between 35 and 80 mg/L. RESULTS: A total of 98 patients (45 obese), with an average weight of 90 (±25) kg, were included. Mean GFR was 84.1 (±40.4) mL/min/1.73 m2. Recommended ceftazidime plasma concentrations were achieved for only 48.0% of patients, with median dosing regimen of 6 g/day. Obese patients had lower ceftazidime plasma concentrations compared with non-obese patients (37.8 versus 56.3 mg/L; P = 0.0042) despite similar dosing regimens (5.83 g/day versus 5.52 g/day, P = 0.2529). Almost all augmented renal clearance patients were underdosed despite ceftazidime dosing of 6.6 (±0.8) g/day. Weight-based ceftazidime dosing seemed to attenuate such obesity-related discrepancies, regardless of GFR. CONCLUSIONS: Obese ICU patients required significantly greater ceftazidime doses to achieve the target range. A tailored dosing regimen may be considered based on weight and GFR. Future prospective studies should be performed to confirm this individualized dosing approach.

Quick Assessment of the Lower Limit of Cerebral Autoregulation Using Transcranial Doppler during Cardiopulmonary Bypass in Cardiac Surgery: A Feasibility Study.

Background: During cardiac surgery, maintaining a mean arterial pressure (MAP) within the range of cerebral autoregulation (CA) may prevent postoperative morbidity. The lower limit of cerebral autoregulation (LLA) can be determined using the mean velocity index (Mx). The standard Mx is averaged over a ten second period ( Mx 10s ) while using a two second averaging period ( Mx 2s ) is faster and may record more rapid variations in LLA. The objective of this study is to compare a quick determination of LLA (qLLA) using Mx 2s with the reference LLA (rLLA) using Mx 10s . Methods: Single center, retrospective, observational study. Patients undergoing cardiac surgery with cardiopulmonary bypass. From January 2020 to April 2021, perioperative transcranial doppler measuring cerebral artery velocity was placed on cardiac surgery patients in order to correlate with continuous MAP values. Calculation of each patient's Mx was manually determined after the surgery and qLLA and rLLA were then calculated using a threshold value of Mx > 0.4. Results: 55 patients were included. qLLA was found in 78% of the cases versus 47% for rLLA. Despite a -3 mmHg mean bias, limits of agreement were large [-19 mmHg (95% CI: -13; -25), and +13 mmHg (95% CI: +6; +19)]. There was an important interobserver variability (kappa rLLA = 0.46; 95% CI: 0.24-0.66; and Kappa qLLA = 0.36; 95% CI: 0.20-0.52). Conclusions: Calculation of qLLA is feasible. However, the large limits of agreement and significant interobserver variability prevent any clinical utility or interchangeability with rLLA.

Diagnostic accuracy of the peripheral venous pressure variation induced by an alveolar recruitment maneuver to predict fluid responsiveness during high-risk abdominal surgery.

BACKGROUND: In patients undergoing high-risk surgery, it is recommended to titrate fluid administration using stroke volume or a dynamic variable of fluid responsiveness (FR). However, this strategy usually requires the use of a hemodynamic monitor and/or an arterial catheter. Recently, it has been shown that variations of central venous pressure (ΔCVP) during an alveolar recruitment maneuver (ARM) can predict FR and that there is a correlation between CVP and peripheral venous pressure (PVP). This prospective study tested the hypothesis that variations of PVP (ΔPVP) induced by an ARM could predict FR. METHODS: We studied 60 consecutive patients scheduled for high-risk abdominal surgery, excluding those with preoperative cardiac arrhythmias or right ventricular dysfunction. All patients had a peripheral venous catheter, a central venous catheter and a radial arterial catheter linked to a pulse contour monitoring device. PVP was always measured via an 18-gauge catheter inserted at the antecubital fossa. Then an ARM consisting of a standardized gas insufflation to reach a plateau of 30 cmH2O for 30 s was performed before skin incision. Invasive mean arterial pressure (MAP), pulse pressure, heart rate, CVP, PVP, pulse pressure variation (PPV), and stroke volume index (SVI) were recorded before ARM (T1), at the end of ARM (T2), before volume expansion (T3), and one minute after volume expansion (T4). Receiver-operating curves (ROC) analysis with the corresponding grey zone approach were performed to assess the ability of ∆PVP (index test) to predict FR, defined as an ≥ 10% increase in SVI following the administration of a 4 ml/kg balanced crystalloid solution over 5 min. RESULTS: ∆PVP during ARM predicted FR with an area under the ROC curve of 0.76 (95%CI, 0.63 to 0.86). The optimal threshold determined by the Youden Index was a ∆PVP value of 5 mmHg (95%CI, 4 to 6) with a sensitivity of 66% (95%CI, 47 to 81) and a specificity of 82% (95%CI, 63 to 94). The AUC's for predicting FR were not different between ΔPVP, ΔCVP, and PPV. CONCLUSION: During high-risk abdominal surgery, ∆PVP induced by an ARM can moderately predict FR. Nevertheless, other hemodynamic variables did not perform better.

Development of normal pressure hydrocephalus following post-traumatic external hydrocephalus in an adult patient.

We report the case of 74-year-old patient suspected of post-traumatic external hydrocephalus (EH) following a mild traumatic brain injury with a progressive neurological decline and a concomitant enlargement of subarachnoid spaces without ventriculomegaly on CT scan. A lumbar puncture revealed raised ICP and a careful CSF withdrawal was performed, resulting in an immediate neurological improvement, confirming the diagnosis of EH. During the 20-month follow-up, the patient presented progressive signs of normal pressure hydrocephalus (NPH): gait and cognitive decline, ventriculomegaly and the lumbar infusion study confirmed disturbed CSF dynamics. The patient underwent a ventriculoperitoneal shunt surgery, resulting in a long-lasting improvement.

A Deep Learning-Based Automated Framework for Subpeak Designation on Intracranial Pressure Signals.

The intracranial pressure (ICP) signal, as monitored on patients in intensive care units, contains pulses of cardiac origin, where P1 and P2 subpeaks can often be observed. When calculable, the ratio of their relative amplitudes is an indicator of the patient's cerebral compliance. This characterization is particularly informative for the overall state of the cerebrospinal system. The aim of this study is to develop and assess the performances of a deep learning-based pipeline for P2/P1 ratio computation that only takes a raw ICP signal as an input. The output P2/P1 ratio signal can be discontinuous since P1 and P2 subpeaks are not always visible. The proposed pipeline performs four tasks, namely (i) heartbeat-induced pulse detection, (ii) pulse selection, (iii) P1 and P2 designation, and (iv) signal smoothing and outlier removal. For tasks (i) and (ii), the performance of a recurrent neural network is compared to that of a convolutional neural network. The final algorithm is evaluated on a 4344-pulse testing dataset sampled from 10 patient recordings. Pulse selection is achieved with an area under the curve of 0.90, whereas the subpeak designation algorithm identifies pulses with a P2/P1 ratio > 1 with 97.3% accuracy. Although it still needs to be evaluated on a larger number of labeled recordings, our automated P2/P1 ratio calculation framework appears to be a promising tool that can be easily embedded into bedside monitoring devices.

Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients.

OBJECTIVES: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration. DESIGN: Prospective nonrandomized study. SETTING: Patients hospitalized in ICU for COVID-19 infection. PATIENTS: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status. CONCLUSIONS: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

Variations of pulse pressure and central venous pressure may predict fluid responsiveness in mechanically ventilated patients during lung recruitment manoeuvre: an ancillary study.

BACKGROUND: Maintaining a constant driving pressure during a prolonged sigh breath lung recruitment manoeuvre (LRM) from 20 to 45 cmH20 peak inspiratory pressure in mechanically ventilated patients has been shown to be a functional test to predict fluid responsiveness (FR) when using a linear regression model of hemodynamic parameters, such as central venous pressure (CVP) and pulse pressure (PP). However, two important limitations have been raised, the use of high ventilation pressures and a regression slope calculation that is difficult to apply at bedside. This ancillary study aimed to reanalyse absolute variations of CVP (ΔCVP) and PP (ΔPP) values at lower stages of the LRM, (40, 35, and 30 cm H20 of peak inspiratory pressure) for their ability to predict fluid responsiveness. METHODS: Retrospective analysis of a prospective study data set in 18 mechanically ventilated patients, in an intensive care unit. CVP, systemic arterial pressure parameters and stroke volume (SV) were recorded during prolonged LRM followed by a 500 mL crystalloid volume expansion. Patients were considered as fluid responders if SV increased more than 10%. Receiver-operating curves (ROC) analysis with the corresponding grey zone approach were performed. RESULTS: Areas under the ROC to predict fluid responsiveness for ΔCVP and ΔPP were not different between the successive stepwise increase of inspiratory pressures [0.88 and 0.89 for ΔCVP at 45 and 30 cm H20 (P = 0.89), respectively, and 0.92 and 0.95 for ΔPP at 45 and 30 cm H20, respectively (P = 0.51)]. Using a maximum of 30 cmH2O inspiratory pressure during the LRM, ΔCVP and ΔPP had a threshold value to predict fluid responsiveness of 2 mmHg and 4 mmHg, with sensitivities of 89% and 89% and specificities of 67% and 89%, respectively. Combining ΔPP and ΔCVP decreased the proportion of the patients in the grey zone from 28 to 11% and showed a sensitivity of 88% and a specificity of 83%. CONCLUSIONS: A stepwise PEEP elevation recruitment manoeuvre of up to 30 cm H20 may predict fluid responsiveness as well as 45 cm H20. The combination of ΔPP and ΔCVP optimizes the categorization of responder and non-responder patients.

Slope analysis for the prediction of fluid responsiveness by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients.

OBJECTIVE: Assessment of fluid responsiveness is problematic in intensive care unit patients. Lung recruitment maneuvers (LRM) can be used as a functional test to predict fluid responsiveness. We propose a new test to predict fluid responsiveness in mechanically ventilated patients by analyzing the variations in central venous pressure (CVP) and systemic arterial parameters during a prolonged sigh breath LRM without the use of a cardiac output measuring device. DESIGN: Prospective observational cohort study. SETTING: Intensive Care Unit, Saint-Etienne University Central Hospital. PATIENTS: Patients under mechanical ventilation, equipped with invasive arterial blood pressure, CVP, pulse contour analysis (PICCO™), requiring volume expansion, with no right ventricular dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CVP, systemic arterial parameters and stroke volume (SV) were recorded during prolonged LRM followed by a 500 mL fluid expansion to asses fluid responsiveness. 25 patients were screened and 18 patients analyzed. 9 patients were responders to volume expansion and 9 were not. Evaluation of hemodynamic parameters suggested the use of a linear regression model. Slopes for systolic arterial pressure, pulse pressure (PP), CVP and SV were all significantly different between responders and non-responders during the pressure increase phase of LRM (STEP-UP) (p = 0.022, p = 0.014, p = 0.006 and p = 0.038, respectively). PP and CVP slopes during STEP-UP were strongly predictive of fluid responsiveness with an AUC of 0.926 (95% CI, 0.78 to 1.00), sensitivity = 100%, specificity = 89% and an AUC = 0.901 (95% CI, 0.76 to 1.00), sensibility = 78%, specificity = 100%, respectively. Combining sensitivity of PP and specificity of CVP, prediction of fluid responsiveness can be achieved with 100% sensitivity and 100% specificity (AUC = 0.96; 95% CI, 0.90 to 1.00). One patient showed inconclusive values using the grey zone approach (5.5%). CONCLUSIONS: In patients under mechanical ventilation with no right heart dysfunction, the association of PP and CVP slope analysis during a prolonged sigh breath LRM seems to offer a very promising method for prediction of fluid responsiveness without the use and associated cost of a cardiac output measurement device. TRIAL REGISTRATION: NCT04304521 , IRBN902018/CHUSTE. Registered 11 March 2020, Fluid responsiveness predicted by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients (STEP-PEEP).

Postural Regulation of Intracranial Pressure: A Critical Review of the Literature.

INTRODUCTION: Mechanisms underlying postural regulation of ICP remain unclear. METHOD: Literature review in Medline 1900-2019 with search terms "Intracranial pressure," "Posture," "Jugular vein," "Collapse," "Regulation," "Physiology," resulting in 40 selected papers. RESULTS: Postural transition from supine to sitting position results in a biphasic decrease of ICP: a fast decrease during phase 1 (low tilt) followed by a stabilization during phase 2 (higher tilt/erect). Two main factors have been proposed to explain this decrease: (a) Fast CSF transfers from the non-distensible cranial compartment to the distensible spinal compartment during phase 1; the maximal spinal expansion corresponds to phase 2; (b) The gravitational effect within the venous system is transferred to the CSF system according to Davson's equation, modulated by jugular collapse that would be responsible for the stabilization of ICP decrease in phase 2. DISCUSSION: The impact of CSF transfers, from the cranial to spinal compartment, on postural regulation of ICP, has been well documented. Although they are sophisticated, models that support the major influence of jugular collapse likely underestimate the role of the vertebral venous plexus in cerebral venous outflow in the upright position. Moreover, Davson's equation supports slow CSF transfer from subarachnoid spaces to the venous system (a few mL/min) and thus cannot explain fast postural modulation of ICP (in a few seconds). Further data are thus needed to better understand postural regulation of ICP.

Quick Assessment of the Lower Limit of Autoregulation by Use of Transcranial Doppler Ultrasound During Cardiac Surgery.

INTRODUCTION: Assessment of the individual safest minimal mean arterial pressure (MAP) during cardiac surgery remains empirical. The objective of this study was to evaluate the lower limit of autoregulation (LLA) within a short period (15 min). METHODS: After developing autoregulation software (OptiMAP) incorporated into transcranial Doppler ultrasound (Waki-Atys®, Lyon, France), we monitored the mean blood flow velocity (MV) and MAP. Thirty successive values of MV and MAP were automatically analysed to calculate the correlation (Mx) between the two parameters. We compared two methods of Mx sampling during a period of 15 min: Mx10s = long averaging windows (one MAP/MV pair recorded every 10 s), and Mx2s = short averaging windows (one MAP/MV pair recorded every 2 s). The LLA value calculated from the whole recording (Mx10s) was used as the reference. Autoregulation was considered impaired at an Mx value >0.35. RESULTS: Five patients were included in the study. The surgery lasted for 138 ± 32 min and cardiopulmonary bypass lasted for 72 ± 33 min. MAP and MV were recorded for 117 ± 24 min. MAP varied from 33 ± 10 to 92 ± 10 mmHg. LLA calculated from the whole recording (Mx10s) was similar to LLA calculated from the 15-min recording (Mx2s): 70 ± 2.5 versus 73 ± 3.5 mmHg. MAP remained below LLA during 48 ± 12% of the recording. During the 15-min recording, Mx10s was not able to calculate the LLA value. CONCLUSION: In cases of haemodynamic instability, decreasing the Mx sampling window seems to accurately detect LLA.

Assessment of Pressure-Volume Index During Lumbar Infusion Study: What Is the Optimal Method?

INTRODUCTION: Assessment of the pressure-volume index (PVI) during lumbar infusion study (LIS) has been proposed to evaluate the overall compliance of the cranio-spinal system. It is calculated from the measurement of CSF pressure changes, ΔP from Pb to Pp, in response to repeated bolus injections of a volume (ΔV) within the lumbar subarachnoid space. MATERIAL AND METHODS: We retrospectively analyzed 18 patients who underwent LIS for suspicion of normal pressure hydrocephalus, including a series of three fast bolus injections of 3 mL of saline at different levels of CSF pressure. We compared two methods for PVI calculation: (a) PVIslope using the slope α of a linear fit ΔP = α(Pb - P 0), PVI = ΔV/log10(α + 1); (b) PVImean using the PVI calculated independently for each bolus injection assuming P 0 = 0, PVI = mean(ΔV/log10(Ppi/Pbi))i=1.3. RESULTS: We found a significant discrepancy between the two methods: the average difference (PVIslope - PVImean) was -3.93 mL (95% confidence interval [8.77; -16.64]). In the PVIslope, method, the mean P 0 was 2.12 mmHg (±3.41 mmHg). DISCUSSION: The clinical reliability of PVImean (assuming P 0 = 0) depends on the value of P 0. PVIslope provides results, independent of P 0. Future studies should focus on determining pathological PVI range rather than fixed cut-off values.

Should the Impact of Postural Change of Intracranial Pressure After Surgical Repair of Skull Base Cerebrospinal Fluid Leaks Be Considered? A Preliminary Survey.

INTRODUCTION: Managing skull base cerebrospinal fluid (CSF) leaks is often challenging. Postoperative care, especially regarding postural restrictions and bedrest recommendations, is variable and continues to be based on empirical habits. METHODS: An electronic survey was submitted to French experts in skull base surgery to evaluate current practice of postoperative postural recommendations in patients treated for skull base CSF leaks. RESULTS: Thirty-nine experts completed the survey. Postoperative recommendations were heterogenous. They depended on the size of defects: half of the surgeons did not recommend any constraints of posture for small defects; 84% recommended bed rest for large defects. The most preferred bed-rest modality was Fowler's position (20°-30° tilt). Standing/walking during short periods was allowed in up to 73%. From a physiological viewpoint, head elevation decreases ICP and thus limits the risk of recurrence of CSF leak. However, ICP can fall below 0 in the standing position, favouring pneumocephalus. DISCUSSION: These results confirmed that postural recommendations for patients surgically treated for skull base CSF leaks remain variable. Recommendations should take into consideration the postural change in ICP. Fowler's position may represent the best compromise between risk of recurrence of CSF leak and the risk of pneumocephalus in large CSF leaks.

External Hydrocephalus After Traumatic Brain Injury: Retrospective Study of 102 Patients.

INTRODUCTION: External hydrocephalus (EH) refers to impairment of extra-axial cerebrospinal fluid flow with enlargement of the subarachnoid space (SAS) and concomitant raised intracranial pressure (ICP). It is often confused with a subdural hygroma and overlooked, particularly when there is no ventricular enlargement. In this study, we aimed to describe the epidemiology of EH in a large population of adults with traumatic brain injury (TBI). METHODS: This observational, retrospective cohort study was conducted in adult patients who were admitted with TBI to the Department of Clinical Neuroscience at Addenbrooke's Hospital (Cambridge, UK) over a period of 3 years (2014-2017). Patients were included in the study if they had ICP monitoring and at least three CT scans within the first 21 days to assess SAS evolution. Patients who underwent a decompressive craniectomy were excluded. SAS was assessed individually on each CT scan by two independent investigators. ICP data were analysed with ICM+ software (Cambridge Enterprise Ltd., Cambridge, UK). Short-term and 6-month outcomes were examined. The groups of patients with and without EH were compared. RESULTS: Of the 102 patients included in the study, 30.4% developed EH after a delay of 2.98 ± 2.4 days. The initial Glasgow Coma Scale (GCS) scores did not differ between patients with and without EH. Subarachnoid haemorrhage was found to be the main risk factor for EH. Patients with EH required a significantly longer period of mechanical ventilation (+6.9 days), were more likely to have a tracheostomy (55% versus 33%), and had a longer stay in the intensive care unit (+8.5 days). ICP was higher during the 48 h after diagnosis of EH than during the previous 48 h. EH survivors had a lower mean Glasgow Outcome Scale Extended (GOS-E) score (4.6 versus 5.9, P = 0.031) and were more likely to receive a permanent shunt for secondary hydrocephalus (17.4% versus 1.8%, odds ratio 7.1). CONCLUSION: In adults with TBI, EH remains insufficiently understood and probably underdiagnosed. This study showed that it is a frequent complication of TBI, with significant clinical consequences.

Differences in Cerebrospinal Fluid Dynamics in Posttraumatic Hydrocephalus Versus Atrophy, Including Effect of Decompression and Cranioplasty.

INTRODUCTION: Challenges in diagnosing post-traumatic hydrocephalus (PTH) have created a need for an accurate diagnostic tool. We aim to report CSF dynamics in PTH and atrophy, along with differences before and after cranioplasty. METHODS: We retrospectively analyzed traumatic brain injury patients with ventriculomegaly who had infusion studies. We divided patients depending on CSF dynamics into two groups: 'likely PTH' (A) and 'likely atrophy' (B). A group of idiopathic normal pressure hydrocephalus shunt-responsive patients was used for comparison (C). RESULTS: Group A consisted of 36 patients who were non-decompressed or had a cranioplasty in situ for over 1 month. Group B included 16 patients with low Rout, AMP, and dAMP, 9 of whom were decompressed. Rout and dAMP were significantly higher in Group A than B, but significantly lower than Group C (45 iNPH patients). RAP change during infusion in group A indicated depleted compensatory reserve compared to ample reserve in group B. Repeat studies in five decompressed patients post-cranioplasty showed all parameters increased. CONCLUSIONS: Infusion tests are not useful in decompressed patients, whilst cranioplasty allowed differentiation between possible PTH and atrophy. Rout and AMP were significantly lower in PTH compared to iNPH and did not always reflect the degree of hydrocephalus reported on imaging.

Impact of Head-of-Bed Posture on Brain Oxygenation in Patients with Acute Brain Injury: A Prospective Cohort Study.

BACKGROUND: Therapeutic head positioning plays a role in the management of patients with acute brain injury. Although intracranial pressure (ICP) is typically lower in an upright posture than in a flat position, limited data exist concerning the effect of upright positioning on brain oxygenation and circulation. We sought to determine the impact of supine (0°) and semirecumbent (15° and 30°) postures on ICP, brain oxygenation, and brain circulation. METHODS: An observational cohort study was conducted between February 2012 and September 2015. Twenty-three patients with severe acute brain injury were successively observed at head elevations of 30°, 15°, and 0°. Postural-induced changes in ICP, cerebral perfusion pressure, brain tissue oxygenation pressure, and transcranial Doppler findings were simultaneously measured during three repeated experiments: 24 h after admission to the intensive care unit (exp1), 24 h later (exp2), and 96 h later (exp3). Cerebral perfusion pressure, arterial blood gases, hemoglobin content, and body temperature remained unchanged during the three experiments. RESULTS: Using linear random-slope mixed models, we found that during the early phase of acute brain injury (exp1), lowering the head posture from 30° to 15°, and then to 0°, was associated with a gradual mean ICP increase of 2.6 mm Hg (1.4-3.7 mm Hg; P < 0.001); and from 30° to 0°, an increase of 7.4 mm Hg (6.3-8.6 mm Hg; P < 0.001). Furthermore, brain tissue oxygenation pressure and mean blood flow velocity improved when the head posture was lowered from 30° to 0° by 1.2 mm Hg (0.2-2.3 mm Hg) and 4.1 cm/s (0.0-8.2 cm/s), respectively (both P < 0.05). CONCLUSIONS: Changing the positioning of stable patients with acute brain injury resulted in opposite changes of ICP versus brain oxygenation and circulation. This information supports the concept of an individualized approach to head positioning that is based on the multimodal monitoring of brain parameters.

Exercise and colorectal cancer: a systematic review and meta-analysis of exercise safety, feasibility and effectiveness.

BACKGROUND: This meta-analysis evaluated the safety, feasibility and effect of exercise among individuals with colorectal cancer. METHODS: A database search (CINAHL, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing, Science Direct) for randomised, controlled, exercise trials involving individuals with colorectal cancer, published before January 1, 2020 was undertaken. Safety (adverse events), feasibility (withdrawal and adherence rates) and effect data (health outcomes including quality of life, QoL) were abstracted. Risk difference (RD) and standardised mean differences (SMD) were calculated to compare safety and effects between exercise and usual care (UC). Subgroup analyses were conducted to assess whether outcomes differed by exercise mode, duration, supervision and treatment. Risk of bias was assessed using the Physiotherapy Evidence Database tool. RESULTS: For the 19 trials included, there was no difference in adverse event risk between exercise and UC (RD = 0.00; 95% CI:-0.01, 0.01, p = 0.92). Median withdrawal rate was 12% (0-22%) and adherence was 86% (42-91%). Significant effects of exercise compared to UC were observed for QoL, fatigue, aerobic fitness, upper-body strength, depression, sleep and reduced body fat (SMD = 0.21-0.66, p < 0.05). Subgroup analyses suggested larger benefits (p < 0.05) for QoL and fatigue for supervised interventions; for QoL, aerobic fitness and reduced body fat for ≥12-week interventions; and for aerobic fitness when interventions were during chemotherapy. CONCLUSION: Although reporting of safety and compliance data was lacking in most trials, findings support that exercise is safe and feasible in colorectal cancer. Further, participation in mixed-mode exercise, including unsupervised exercise, leads to improvements in various health-related outcomes.

Validation of Davson's equation in patients suffering from idiopathic normal pressure hydrocephalus.

INTRODUCTION: The so-called Davson's equation relates baseline intracranial pressure (ICP) to resistance to cerebrospinal fluid outflow (Rout), formation of cerebrospinal fluid (If) and sagittal sinus pressure (PSS) There is a controversy over whether this fundamental equation is applicable in patients with normal pressure hydrocephalus (NPH). We investigated the relationship between Rout and ICP and also other compensatory, clinical and demographic parameters in NPH patients. METHOD: We carried out a retrospective study of 229 patients with primary NPH who had undergone constant-rate infusion studies in our hospital. Data was recorded and processed using ICM+ software. Relationships between variables were sought by calculating Pearson product correlation coefficients and p values. RESULTS: We found a significant, albeit weak, relationship between ICP and Rout (R = 0.17, p = 0.0049), Rout and peak-to-peak amplitude of ICP (AMP) (R = 0.27, p = 3.577e-05) and Rout and age (R = 0.16, p = 0.01306). CONCLUSIONS: The relationship found between ICP and Rout provides indirect evidence to support disturbed Cerebrospinal fluid circulation as a key factor in disturbed CSF dynamics in NPH. Weak correlation may indicate that other factors-variable PSS and formation of CSF outflow-contribute heavily to linear model expressed by Davson's equation.

Using external lumbar CSF drainage to treat communicating external hydrocephalus in adult patients after acute traumatic or non-traumatic brain injury.

BACKGROUND: Despite various treatments to control intracranial pressure (ICP) after brain injury, patients may present a late onset of high ICP or a poor response to medications. External lumbar drainage (ELD) can be considered a therapeutic option if high ICP is due to communicating external hydrocephalus. We aimed at describing the efficacy and safety of ELD used in a cohort of traumatic or non-traumatic brain-injured patients. METHODS: In this multicentre retrospective analysis, patients had a delayed onset of high ICP after the initial injury and/or a poor response to ICP treatments. ELD was considered in the presence of radiological signs of communicating external hydrocephalus. Changes in ICP values and side effects following the ELD procedure were reported. RESULTS: Thirty-three patients with a median age of 51 years (25-75th percentile: 34-61 years) were admitted after traumatic (n = 22) or non-traumatic (n = 11) brain injuries. Their initial Glasgow Coma Scale score was 8 (4-11). Eight patients underwent external ventricular drainage prior to ELD. Median time to ELD insertion was 5 days (4-8) after brain insult. In all patients, ELD was dramatically effective in lowering ICP: 25 mmHg (20-31) before versus 7 mmHg (3-10) after (p < 0.001). None of the patients showed adverse effects such as pupil changes or intracranial bleeding after the procedure. One patient developed an ELD-related infection. CONCLUSIONS: These findings indicate that ELD may be considered potentially effective in controlling ICP, remaining safe if a firm diagnosis of communicating external hydrocephalus has been made.

The venous-arterial difference in CO2 should be interpreted with caution in case of respiratory alkalosis in healthy volunteers.

The venous-arterial difference in CO2 (ΔCO2) has been proposed as an index of the adequacy of tissue perfusion in shock states. We hypothesized that the variation in PaCO2 (hyper- or hypocapnia) could impact ΔCO2, partly through microcirculation adaptations. Fifteen healthy males volunteered to participate. For hypocapnia condition (hCO2), the subjects were asked to hyperventilate, while they were asked to breathe a gas mixture containing 8 % CO2 for hypercapnia condition (HCO2). The 2 conditions were randomly assigned. Blood gases were measured at baseline before each condition, and after 5-7 min of either hCO2 or HCO2 condition. Microcirculation was assessed by the muscle reoxygenation slope measured with near infrared spectroscopy following a vascular occlusion test and by skin circulation with in vivo reflectance confocal microscopy. ΔCO2 was significantly increased with hCO2 while it tended to decrease with HCO2 (non-significant). HCO2 induced a moderate increase of the resaturation slope of NIRS oxygenation. Skin microcirculatory blood flow significantly dropped with hCO2, while it remained unchanged with hypercapnia. Our results warrant cautious interpretation of ΔCO2 as an indicator of tissue perfusion during respiratory alkalosis.

Assessment of CSF Dynamics Using Infusion Study: Tips and Tricks.

Idiopathic normal pressure hydrocephalus, secondary chronic hydrocephalus, and other cerebrospinal fluid (CSF) disorders are often challenging to diagnose. Since shunt surgery is usually the only therapeutic option and carries significant morbidity, optimal patient selection is crucial. The tap test is the most commonly used prognostic test to confirm the diagnosis but lacks sensitivity. The lumbar infusion study (LIS) appears to be a better option, offering additional information on brain dynamics without increasing morbidity. However, this technique remains underused. In this narrative review, supported by the extensive experience of several European expert centers, we detail the physiological basis, indications, and CSF dynamics parameters that can be measured. We also discuss technical modalities and variations, including one versus 2 needles, patient positioning, and the site of CSF measurement, as well as in vivo shunt testing. Finally, we discuss the limitations and morbidity associated with the LIS. This review aims to assist teams wishing to incorporate LIS into their screening tools for chronic hydrocephalus and other CSF disorders.