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  1. Article ; Online: Tracheal intubation in traumatic brain injury: a multicentre prospective observational study.

    Gravesteijn, Benjamin Yael / Sewalt, Charlie Aletta / Nieboer, Daan / Menon, David Krishna / Maas, Andrew / Lecky, Fiona / Klimek, Markus / Lingsma, Hester Floor

    British journal of anaesthesia

    2020  Volume 125, Issue 4, Page(s) 505–517

    Abstract: Background: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity.: Methods: Data from the international ... ...

    Abstract Background: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity.
    Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests.
    Results: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio=1.01; 95% confidence interval, 0.79-1.28; P=0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio=0.86; 95% confidence interval, 0.65-1.13; P=0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P=0.009 and P=0.02, respectively), whereas in-hospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P=0.01): in-hospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower.
    Conclusion: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting.
    Clinical trial registration: NCT02210221.
    MeSH term(s) Adult ; Aged ; Brain Injuries, Traumatic/surgery ; Female ; Humans ; Intubation, Intratracheal/methods ; Male ; Middle Aged ; Prospective Studies ; Trauma Severity Indices
    Language English
    Publishing date 2020-07-31
    Publishing country England
    Document type Journal Article ; Multicenter Study ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 80074-0
    ISSN 1471-6771 ; 0007-0912
    ISSN (online) 1471-6771
    ISSN 0007-0912
    DOI 10.1016/j.bja.2020.05.067
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  2. Article ; Online: Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI): a prospective, multicentre, comparative effectiveness study.

    Wiegers, Eveline Janine Anna / Lingsma, Hester Floor / Huijben, Jilske Antonia / Cooper, David James / Citerio, Giuseppe / Frisvold, Shirin / Helbok, Raimund / Maas, Andrew Ian Ramsay / Menon, David Krishna / Moore, Elizabeth Madeleine / Stocchetti, Nino / Dippel, Diederik Willem / Steyerberg, Ewout Willem / van der Jagt, Mathieu

    The Lancet. Neurology

    2021  Volume 20, Issue 8, Page(s) 627–638

    Abstract: Background: Fluid therapy-the administration of fluids to maintain adequate organ tissue perfusion and oxygenation-is essential in patients admitted to the intensive care unit (ICU) with traumatic brain injury. We aimed to quantify the variability in ... ...

    Abstract Background: Fluid therapy-the administration of fluids to maintain adequate organ tissue perfusion and oxygenation-is essential in patients admitted to the intensive care unit (ICU) with traumatic brain injury. We aimed to quantify the variability in fluid management policies in patients with traumatic brain injury and to study the effect of this variability on patients' outcomes.
    Methods: We did a prospective, multicentre, comparative effectiveness study of two observational cohorts: CENTER-TBI in Europe and OzENTER-TBI in Australia. Patients from 55 hospitals in 18 countries, aged 16 years or older with traumatic brain injury requiring a head CT, and admitted to the ICU were included in this analysis. We extracted data on demographics, injury, and clinical and treatment characteristics, and calculated the mean daily fluid balance (difference between fluid input and loss) and mean daily fluid input during ICU stay per patient. We analysed the association of fluid balance and input with ICU mortality and functional outcome at 6 months, measured by the Glasgow Outcome Scale Extended (GOSE). Patient-level analyses relied on adjustment for key characteristics per patient, whereas centre-level analyses used the centre as the instrumental variable.
    Findings: 2125 patients enrolled in CENTER-TBI and OzENTER-TBI between Dec 19, 2014, and Dec 17, 2017, were eligible for inclusion in this analysis. The median age was 50 years (IQR 31 to 66) and 1566 (74%) of patients were male. The median of the mean daily fluid input ranged from 1·48 L (IQR 1·12 to 2·09) to 4·23 L (3·78 to 4·94) across centres. The median of the mean daily fluid balance ranged from -0·85 L (IQR -1·51 to -0·49) to 1·13 L (0·99 to 1·37) across centres. In patient-level analyses, a mean positive daily fluid balance was associated with higher ICU mortality (odds ratio [OR] 1·10 [95% CI 1·07 to 1·12] per 0·1 L increase) and worse functional outcome (1·04 [1·02 to 1·05] per 0·1 L increase); higher mean daily fluid input was also associated with higher ICU mortality (1·05 [1·03 to 1·06] per 0·1 L increase) and worse functional outcome (1·04 [1·03 to 1·04] per 1-point decrease of the GOSE per 0·1 L increase). Centre-level analyses showed similar associations of higher fluid balance with ICU mortality (OR 1·17 [95% CI 1·05 to 1·29]) and worse functional outcome (1·07 [1·02 to 1·13]), but higher fluid input was not associated with ICU mortality (OR 0·95 [0·90 to 1·00]) or worse functional outcome (1·01 [0·98 to 1·03]).
    Interpretation: In critically ill patients with traumatic brain injury, there is significant variability in fluid management, with more positive fluid balances being associated with worse outcomes. These results, when added to previous evidence, suggest that aiming for neutral fluid balances, indicating a state of normovolaemia, contributes to improved outcome.
    Funding: European Commission 7th Framework program and the Australian Health and Medical Research Council.
    MeSH term(s) Adult ; Aged ; Brain Injuries, Traumatic/metabolism ; Brain Injuries, Traumatic/mortality ; Cohort Studies ; Critical Care ; Critical Illness ; Female ; Fluid Therapy/methods ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Humans ; Male ; Middle Aged ; Prospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome ; Water-Electrolyte Balance
    Language English
    Publishing date 2021-07-22
    Publishing country England
    Document type Comparative Study ; Journal Article ; Multicenter Study ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2081241-3
    ISSN 1474-4465 ; 1474-4422
    ISSN (online) 1474-4465
    ISSN 1474-4422
    DOI 10.1016/S1474-4422(21)00162-9
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  3. Article ; Online: Physostigmine for prevention of postoperative delirium and long-term cognitive dysfunction in liver surgery: A double-blinded randomised controlled trial.

    Spies, Claudia D / Knaak, Cornelia / Mertens, Mandy / Brockhaus, Wolf-Rüdiger / Shadenok, Anna / Wiebach, Janine / Kunzmann, Kevin / Feldheiser, Aarne / Pratschke, Johann / Müller, Olga / Kipping, Valesca / Fabian, Maria / Abels, Wiltrud / Borchers, Friedrich / Akyüz, Levent / Ely, E Wesley / Wernecke, Klaus-Dieter / Menon, David Krishna / Piper, Sophie K

    European journal of anaesthesiology

    2021  Volume 38, Issue 9, Page(s) 943–956

    Abstract: Background: Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction.: Objective: The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) ... ...

    Abstract Background: Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction.
    Objective: The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing liver resection.
    Design: This was a double-blind, randomised, placebo-controlled trial. Between 11 August 2009 and 3 March 2016, patients were recruited at the Charité - Universitätsmedizin Berlin in Germany. Follow-ups took place at 1 week (T1), 90 days (T2) and 365 days (T3) after surgery.
    Setting: This single-centre study was conducted at an academic medical centre.
    Participants: In total, 261 participants aged at least 18 years scheduled for elective liver surgery were randomised. The protocol also included 45 non-surgical matched controls to provide normative data for POCD and neurocognitive deficit (NCD).
    Intervention: Participants were allocated to receive either intravenous physostigmine, as a bolus of 0.02 mg kg-1 body weight followed by 0.01 mg kg-1 body weight per hour (n = 130), or placebo (n = 131), for 24 h after induction of anaesthesia.
    Main outcomes and measures: Primary outcomes were POD, assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-4-TR) twice daily up to day 7 after surgery, and POCD assessed via the CANTAB neuropsychological test battery, and two paper pencil tests on the day before surgery, and on postoperative days 7, 90 and 365.
    Results: In total, 261 patients were randomised, 130 to the physostigmine and 131 to the placebo group. The incidence of POD did not differ significantly between the physostigmine and placebo groups (20 versus 15%; P = 0.334). Preoperative cognitive impairment and POCD frequencies did not differ significantly between the physostigmine and placebo groups at any time. Lower mortality rates were found in the physostigmine group compared with placebo at 3 months [2% (95% confidence interval (CI), 0 to 4) versus 11% (95% CI, 6 to 16), P = 0.002], and 6 months [7% (95% CI, 3 to 12) versus 16% (95% CI, 10 to 23), P = 0.012] after surgery.
    Conclusion: Physostigmine had no effect on POD and POCD when applied after induction of anaesthesia up to 24 h.
    Trial registration: DOI 10.1186/ISRCTN18978802, EudraCT 2008-007237-47, Ethics approval ZS EK 11 618/08 (15 January 2009).
    MeSH term(s) Adolescent ; Adult ; Cognitive Dysfunction/epidemiology ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/prevention & control ; Delirium/diagnosis ; Delirium/epidemiology ; Delirium/prevention & control ; Humans ; Liver ; Physostigmine ; Postoperative Complications/epidemiology ; Postoperative Complications/prevention & control
    Chemical Substances Physostigmine (9U1VM840SP)
    Language English
    Publishing date 2021-01-27
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 605770-6
    ISSN 1365-2346 ; 0265-0215
    ISSN (online) 1365-2346
    ISSN 0265-0215
    DOI 10.1097/EJA.0000000000001456
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  4. Article: Variability in the concentrations of intravenous drug infusions prepared in a critical care unit.

    Wheeler, Daniel Wren / Degnan, Beverley Ann / Sehmi, Jobanpreet Singh / Burnstein, Rowan Margaret / Menon, David Krishna / Gupta, Arun Kumar

    Intensive care medicine

    2008  Volume 34, Issue 8, Page(s) 1441–1447

    Abstract: Objective: To quantify the variability in the concentration of drug infusions prepared on an intensive care unit and establish whether there was a relationship between the quality of syringe labeling and drug preparation.: Design: Audit carried out ... ...

    Abstract Objective: To quantify the variability in the concentration of drug infusions prepared on an intensive care unit and establish whether there was a relationship between the quality of syringe labeling and drug preparation.
    Design: Audit carried out over 3 weeks in May 2006 and completed in May 2007.
    Setting: The adult neurosciences critical care unit of a UK university teaching hospital.
    Interventions: Daily collections of discarded syringes containing midazolam, insulin, norepinephrine, dopamine, potassium or magnesium.
    Measurements and results: Residual solutions in the syringes were sampled and the concentrations measured. Syringe labels were inspected and awarded a score for labeling quality based on an 11-point scale. A total of 149 syringes were analyzed. Six of the magnesium syringes contained 4-5 times too much Mg(2+), presumably because of confusion about converting millimoles to grams. The majority of the other infusions differed from the expected concentration by more than 10%. Magnesium infusions were least likely to be properly labeled (p= 0.012), and there was a positive correlation between quality of syringe labeling and drug preparation (p=0.002). After the introduction of a new electrolyte prescription chart, magnesium and potassium preparation significantly improved but there was still substantial variability.
    Conclusions: These findings present a strong argument for the use of pre-prepared syringes or standardized drug preparation and labeling systems. They also highlight once again the difficulties healthcare professionals encounter when dealing with different ways of expressing drug concentrations.
    MeSH term(s) Anticonvulsants/administration & dosage ; Drug Labeling ; Electrolytes/administration & dosage ; Humans ; Infusions, Intravenous ; Intensive Care Units/statistics & numerical data ; Magnesium Sulfate/administration & dosage ; Medical Audit/methods ; Medical Audit/statistics & numerical data ; Medication Errors/prevention & control ; Medication Errors/statistics & numerical data ; Syringes ; United Kingdom
    Chemical Substances Anticonvulsants ; Electrolytes ; Magnesium Sulfate (7487-88-9)
    Language English
    Publishing date 2008-04-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80387-x
    ISSN 1432-1238 ; 0342-4642 ; 0340-0964 ; 0935-1701
    ISSN (online) 1432-1238
    ISSN 0342-4642 ; 0340-0964 ; 0935-1701
    DOI 10.1007/s00134-008-1113-9
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  5. Article ; Online: Individualizing Thresholds of Cerebral Perfusion Pressure Using Estimated Limits of Autoregulation.

    Donnelly, Joseph / Czosnyka, Marek / Adams, Hadie / Robba, Chiara / Steiner, Luzius A / Cardim, Danilo / Cabella, Brenno / Liu, Xiuyun / Ercole, Ari / Hutchinson, Peter John / Menon, David Krishna / Aries, Marcel J H / Smielewski, Peter

    Critical care medicine

    2012  Volume 45, Issue 9, Page(s) 1464–1471

    Abstract: Objectives: In severe traumatic brain injury, cerebral perfusion pressure management based on cerebrovascular pressure reactivity index has the potential to provide a personalized treatment target to improve patient outcomes. So far, the methods have ... ...

    Abstract Objectives: In severe traumatic brain injury, cerebral perfusion pressure management based on cerebrovascular pressure reactivity index has the potential to provide a personalized treatment target to improve patient outcomes. So far, the methods have focused on identifying "one" autoregulation-guided cerebral perfusion pressure target-called "cerebral perfusion pressure optimal". We investigated whether a cerebral perfusion pressure autoregulation range-which uses a continuous estimation of the "lower" and "upper" cerebral perfusion pressure limits of cerebrovascular pressure autoregulation (assessed with pressure reactivity index)-has prognostic value.
    Design: Single-center retrospective analysis of prospectively collected data.
    Setting: The neurocritical care unit at a tertiary academic medical center.
    Patients: Data from 729 severe traumatic brain injury patients admitted between 1996 and 2016 were used. Treatment was guided by controlling intracranial pressure and cerebral perfusion pressure according to a local protocol.
    Interventions: None.
    Methods and main results: Cerebral perfusion pressure-pressure reactivity index curves were fitted automatically using a previously published curve-fitting heuristic from the relationship between pressure reactivity index and cerebral perfusion pressure. The cerebral perfusion pressure values at which this "U-shaped curve" crossed the fixed threshold from intact to impaired pressure reactivity (pressure reactivity index = 0.3) were denoted automatically the "lower" and "upper" cerebral perfusion pressure limits of reactivity, respectively. The percentage of time with cerebral perfusion pressure below (%cerebral perfusion pressure < lower limit of reactivity), above (%cerebral perfusion pressure > upper limit of reactivity), or within these reactivity limits (%cerebral perfusion pressure within limits of reactivity) was calculated for each patient and compared across dichotomized Glasgow Outcome Scores. After adjusting for age, initial Glasgow Coma Scale, and mean intracranial pressure, percentage of time with cerebral perfusion pressure less than lower limit of reactivity was associated with unfavorable outcome (odds ratio %cerebral perfusion pressure < lower limit of reactivity, 1.04; 95% CI, 1.02-1.06; p < 0.001) and mortality (odds ratio, 1.06; 95% CI, 1.04-1.08; p < 0.001).
    Conclusions: Individualized autoregulation-guided cerebral perfusion pressure management may be a plausible alternative to fixed cerebral perfusion pressure threshold management in severe traumatic brain injury patients. Prospective randomized research will help define which autoregulation-guided method is beneficial, safe, and most practical.
    MeSH term(s) Academic Medical Centers ; Adult ; Age Factors ; Brain Injuries, Traumatic/physiopathology ; Brain Injuries, Traumatic/therapy ; Cerebrovascular Circulation/physiology ; Critical Care/methods ; Female ; Glasgow Coma Scale ; Homeostasis/physiology ; Humans ; Intracranial Pressure/physiology ; Male ; Middle Aged ; Retrospective Studies ; Time Factors
    Language English
    Publishing date 2012-04-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 197890-1
    ISSN 1530-0293 ; 0090-3493
    ISSN (online) 1530-0293
    ISSN 0090-3493
    DOI 10.1097/CCM.0000000000002575
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  6. Article: The MHP36 line of murine neural stem cells expresses functional CXCR1 chemokine receptors that initiate chemotaxis in vitro.

    Beech, John Samuel / Wheeler, Daniel Wren / Reckless, Jill / Grant, Andrew James / Price, Jack / Mastroeni, Pietro / Grainger, David John / Menon, David Krishna

    Journal of neuroimmunology

    2007  Volume 184, Issue 1-2, Page(s) 198–208

    Abstract: Chemokines help to establish cerebral inflammation after ischemia, which comprises a major component of secondary brain injury. The CXCR4 chemokine receptor system induces neural stem cell migration, and hence has been implicated in brain repair. We show ...

    Abstract Chemokines help to establish cerebral inflammation after ischemia, which comprises a major component of secondary brain injury. The CXCR4 chemokine receptor system induces neural stem cell migration, and hence has been implicated in brain repair. We show that CXCR1 and interleukin-8 also stimulate chemotaxis in murine neural stem cells from the MHP36 cell line. The presence of CXCR1 was confirmed by reverse transcriptase PCR and immunohistochemistry. Interleukin-8 evoked intracellular calcium currents, upregulated doublecortin (a protein expressed by migrating neuroblasts), and elicited positive chemotaxis in vitro. Therefore, effectors of the early innate immune response may also influence brain repair mechanisms.
    MeSH term(s) Analysis of Variance ; Animals ; Calcium/metabolism ; Cell Line ; Cell Movement/drug effects ; Cell Movement/physiology ; Chemotaxis/drug effects ; Chemotaxis/physiology ; Dose-Response Relationship, Drug ; Doublecortin Domain Proteins ; Drug Interactions ; Enzyme Inhibitors/pharmacology ; Flow Cytometry/methods ; Gene Expression/drug effects ; Gene Expression/physiology ; Immunohistochemistry/methods ; In Vitro Techniques ; Interleukin-8/pharmacology ; Mice ; Microtubule-Associated Proteins/metabolism ; Neurons/drug effects ; Neurons/metabolism ; Neuropeptides/metabolism ; Peptides, Cyclic/pharmacology ; RNA, Messenger/biosynthesis ; Receptors, Interleukin-8A/genetics ; Receptors, Interleukin-8A/metabolism ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Stem Cells/drug effects ; Stem Cells/metabolism
    Chemical Substances Doublecortin Domain Proteins ; Enzyme Inhibitors ; Interleukin-8 ; Microtubule-Associated Proteins ; Neuropeptides ; Peptides, Cyclic ; RNA, Messenger ; Receptors, Interleukin-8A ; cyclo(cysteinyl-glutaminyl-isoleucyl-tryptophyl-lysyl-glutaminyl-lysyl-prolyl-aspartyl-leucyl-cysteinyl-amide) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2007-02-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 8335-5
    ISSN 1872-8421 ; 0165-5728
    ISSN (online) 1872-8421
    ISSN 0165-5728
    DOI 10.1016/j.jneuroim.2006.12.015
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  7. Article: Doctors' confusion over ratios and percentages in drug solutions: the case for standard labelling.

    Wheeler, Daniel Wren / Remoundos, Dionysios Dennis / Whittlestone, Kim David / Palmer, Michael Ian / Wheeler, Sarah Jane / Ringrose, Timothy Richard / Menon, David Krishna

    Journal of the Royal Society of Medicine

    2004  Volume 97, Issue 8, Page(s) 380–383

    Abstract: The different ways of expressing concentrations of drugs in solution, as ratios or percentages or mass per unit volume, are a potential cause of confusion that may contribute to dose errors. To assess doctors' understanding of what they signify, all ... ...

    Abstract The different ways of expressing concentrations of drugs in solution, as ratios or percentages or mass per unit volume, are a potential cause of confusion that may contribute to dose errors. To assess doctors' understanding of what they signify, all active subscribers to doctors.net.uk, an online community exclusively for UK doctors, were invited to complete a brief web-based multiple-choice questionnaire that explored their familiarity with solutions of adrenaline (expressed as a ratio), lidocaine (expressed as a percentage) and atropine (expressed in mg per mL), and their ability to calculate the correct volume to administer in clinical scenarios relevant to all specialties. 2974 (24.6%) replied. The mean score achieved was 4.80 out of 6 (SD 1.38). Only 85.2% and 65.8% correctly identified the mass of drug in the adrenaline and lidocaine solutions, respectively, whilst 93.1% identified the correct concentration of atropine. More would have administered the correct volume of adrenaline and lidocaine in clinical scenarios (89.4% and 81.0%, respectively) but only 65.5% identified the correct volume of atropine. The labelling of drug solutions as ratios or percentages is antiquated and confusing. Labelling should be standardized to mass per unit volume.
    MeSH term(s) Clinical Competence/standards ; Drug Labeling/standards ; Humans ; Medicine ; Pharmaceutical Solutions/standards ; Physicians/standards ; Specialization ; Surveys and Questionnaires ; United Kingdom
    Chemical Substances Pharmaceutical Solutions
    Language English
    Publishing date 2004-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 6731-3
    ISSN 1758-1095 ; 0141-0768 ; 0035-9157
    ISSN (online) 1758-1095
    ISSN 0141-0768 ; 0035-9157
    DOI 10.1177/014107680409700805
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