Principles of environmentally-sustainable anaesthesia: a global consensus statement from the World Federation of Societies of Anaesthesiologists.

The Earth's mean surface temperature is already approximately 1.1°C higher than pre-industrial levels. Exceeding a mean 1.5°C rise by 2050 will make global adaptation to the consequences of climate change less possible. To protect public health, anaesthesia providers need to reduce the contribution their practice makes to global warming. We convened a Working Group of 45 anaesthesia providers with a recognised interest in sustainability, and used a three-stage modified Delphi consensus process to agree on principles of environmentally sustainable anaesthesia that are achievable worldwide. The Working Group agreed on the following three important underlying statements: patient safety should not be compromised by sustainable anaesthetic practices; high-, middle- and low-income countries should support each other appropriately in delivering sustainable healthcare (including anaesthesia); and healthcare systems should be mandated to reduce their contribution to global warming. We set out seven fundamental principles to guide anaesthesia providers in the move to environmentally sustainable practice, including: choice of medications and equipment; minimising waste and overuse of resources; and addressing environmental sustainability in anaesthetists' education, research, quality improvement and local healthcare leadership activities. These changes are achievable with minimal material resource and financial investment, and should undergo re-evaluation and updates as better evidence is published. This paper discusses each principle individually, and directs readers towards further important references.

Towards high-quality peri-operative care: a global perspective.

Article 25 of the United Nations' Universal Declaration of Human Rights enshrines the right to health and well-being for every individual. However, universal access to high-quality healthcare remains the purview of a handful of wealthy nations. This is no more apparent than in peri-operative care, where an estimated five billion individuals lack access to safe, affordable and timely surgical care. Delivery of surgery and anaesthesia in low-resource environments presents unique challenges that, when unaddressed, result in limited access to low-quality care. Current peri-operative research and clinical guidance often fail to acknowledge these system-level deficits and therefore have limited applicability in low-resource settings. In this manuscript, the authors priority-set the need for equitable access to high-quality peri-operative care and analyse the system-level contributors to excess peri-operative mortality rates, a key marker of quality of care. To provide examples of how research and investment may close the equity gap, a modified Delphi method was adopted to curate and appraise interventions which may, with subsequent research and evaluation, begin to address the barriers to high-quality peri-operative care in low- and middle-income countries.

Anaemia and red blood cell transfusion in intracranial neurosurgery: a comprehensive review.

Both anaemia and blood transfusion are associated with poor outcomes in the neurosurgical population. Based on the available literature, the optimal haemoglobin concentration for neurologically injured patients appears to be in the range of 9.0-10.0 g dl-1, although the individual risks and benefits should be weighed. Several perioperative blood conservation strategies have been used successfully in neurosurgery, including correction of anaemia and coagulopathy, use of antifibrinolytics, and intraoperative cell salvage. Avoidance of non-steroidal anti-inflammatory drugs and starch-containing solutions is recommended given the potential for platelet dysfunction.

Definition, evaluation, and management of brain relaxation during craniotomy.

The term 'brain relaxation' is routinely used to describe the size and firmness of the brain tissue during craniotomy. The status of brain relaxation is an important aspect of neuroanaesthesia practice and is relevant to the operating conditions, retraction injury, and likely patient outcomes. Brain relaxation is determined by the relationship between the volume of the intracranial contents and the capacity of the intracranial space (i.e. a content-space relationship). It is a concept related to, but distinct from, intracranial pressure. The evaluation of brain relaxation should be standardized to facilitate clinical communication and research collaboration. Both advantageous and disadvantageous effects of the various interventions for brain relaxation should be taken into account in patient care. The outcomes that matter the most to patients should be emphasized in defining, evaluating, and managing brain relaxation. To date, brain relaxation has not been reviewed specifically, and the aim of this manuscript is to discuss the current approaches to the definition, evaluation, and management of brain relaxation, knowledge gaps, and targets for future research.

Clinical diagnostic tools for screening of perioperative stroke in general surgery: a systematic review.

Perioperative stroke is a devastating complication that carries high mortality and functional disability. Unfortunately, residual anaesthesia and analgesia may obscure important warning signs and may lead to a delay in the assessment and treatment of major stroke after surgery. The purpose of this review is to examine the utility of existing stroke scales, for the recognition of perioperative stroke in the general surgical population. A total of 21 stroke scales have been described in the literature. Diagnostic performance was reported in 17 scales. The majority of the stroke scales were designed to evaluate current neurological deficits after an established stroke event. Recent abbreviated stroke test, such as the Face, Arm, Speech Test (FAST), were developed to facilitate stroke identification in the emergency department. Only two stroke scales have been applied in the perioperative setting after cardiac, carotid and neurological surgeries. The modified National Institutes of Health Stroke Scale appears to be useful in detecting new subtle neurological deficits in critical care, or high dependency units after surgery. However, in the general postsurgical wards, given the concern about the workload required, abbreviated stroke tests may be more appropriate for routine regular stroke surveillance. It is hoped that these tests will provide rapid assessment of global neurological function to facilitate timely diagnosis and treatment of perioperative stroke.

Covert stroke after non-cardiac surgery: a prospective cohort study.

BACKGROUND: Overt stroke after non-cardiac surgery has a substantial impact on the duration and quality of life. Covert stroke in the non-surgical setting is much more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac, non-carotid artery surgery. METHODS: We undertook a prospective, international cohort study to determine the incidence of covert stroke after non-cardiac, non-carotid artery surgery. Eligible patients were ≥65 yr of age and were admitted to hospital for at least three nights after non-cardiac, non-carotid artery surgery. Patients underwent a brain magnetic resonance study between postoperative days 3 and 10. The main outcome was the incidence of perioperative covert stroke. RESULTS: We enrolled a total of 100 patients from six centres in four countries. The incidence of perioperative covert stroke was 10.0% (10/100 patients, 95% confidence interval 5.5-17.4%). Five of the six centres that enrolled patients reported an incident covert stroke, and covert stroke was found in patients undergoing major general (3/27), major orthopaedic (3/41), major urological or gynaecological (3/22), and low-risk surgery (1/12). CONCLUSIONS: This international multicentre study suggests that 1 in 10 patients ≥65 yr of age experiences a perioperative covert stroke. A larger study is required to determine the impact of perioperative covert stroke on patient-important outcomes. CLINICAL TRIAL REGISTRATION: NCT01369537.

Flurbiprofen and hypertension but not hydroxyethyl starch are associated with post-craniotomy intracranial haematoma requiring surgery.

BACKGROUND: Post-craniotomy intracranial haematoma is one of the most serious complications after neurosurgery. We examined whether post-craniotomy intracranial haematoma requiring surgery is associated with the non-steroidal anti-inflammatory drugs flurbiprofen, hypertension, or hydroxyethyl starch (HES). METHODS: A case-control study was conducted among 42 359 patients who underwent elective craniotomy procedures at Beijing Tiantan Hospital between January 2006 and December 2011. A one-to-one control group without post-craniotomy intracranial haematoma was selected matched by age, pathologic diagnosis, tumour location, and surgeon. Perioperative blood pressure records up to the diagnosis of haematoma, the use of flurbiprofen and HES were examined. The incidence of post-craniotomy intracranial haematoma and the odds ratios for the risk factors were determined. RESULTS: A total of 202 patients suffered post-craniotomy intracranial haematoma during the study period, for an incidence of 0.48% (95% CI=0.41-0.55). Haematoma requiring surgery was associated with an intraoperative systolic blood pressure of >160 mm Hg (OR=2.618, 95% CI=2.084-2.723, P=0.007), an intraoperative mean blood pressure of >110 mm Hg (OR=2.600, 95% CI=2.312-3.098, P=0.037), a postoperative systolic blood pressure of >160 mm Hg (OR=2.060, 95% CI= 1.763-2.642, P=0.022), a postoperative mean blood pressure of >110 mm Hg (OR=3.600, 95% CI= 3.226-4.057, P=0.001), and the use of flurbiprofen during but not after the surgery (OR=2.256, 95% CI=2.004-2.598, P=0.005). The intraoperative infusion of HES showed no significant difference between patients who had a haematoma and those who did not. CONCLUSIONS: Intraoperative and postoperative hypertension and the use of flurbiprofen during surgery are risk factors for post-craniotomy intracranial haematoma requiring surgery. The intraoperative infusion of HES was not associated with a higher incidence of haematoma.

Pharmacological perioperative brain neuroprotection: a qualitative review of randomized clinical trials.

Perioperative cerebral damage may be associated with surgery and anaesthesia. Pharmacological perioperative neuroprotection is associated with conflicting results. In this qualitative review of randomized controlled clinical trials on perioperative pharmacological brain neuroprotection, we report the effects of tested therapies on new postoperative neurological deficit, postoperative cognitive decline (POCD), and mortality rate. Studies were identified from Cochrane Central Register and MEDLINE and by hand-searching. Of 5904 retrieved studies, 25 randomized trials met our inclusion criteria. Tested therapies were: lidocaine, thiopental, S(+)-ketamine, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate and xenon remacemide, atorvastatin, magnesium sulphate, erythropoietin, piracetam, rivastigmine, pegorgotein, and 17ß-estradiol. The use of atorvastatin and magnesium sulphate was associated with a lower incidence of new postoperative neurological deficit. The use of lidocaine, ketamine, and magnesium sulphate was associated with controversial results on POCD. The POCD did not differ between treated patients and control group for other tested drugs (thiopental, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate, xenon, erythropoietin, remacemide, piracetam, rivastigmine, pegorgotein, and 17ß-estradiol). None of the tested drugs was associated with a reduction in mortality rate. Drugs with various mechanisms of action have been tested over time; current evidence suggests that pharmacological brain neuroprotection might reduce the incidence of new postoperative neurological deficits and POCD, while no benefits on perioperative mortality are described. Of importance from this review is the need for shared methodological approach when clinical studies on pharmacological neuroprotection are designed.

Impact of stepwise hyperventilation on cerebral tissue oxygen saturation in anesthetized patients: a mechanistic study.

BACKGROUND: While the decrease in blood carbon dioxide (CO2 ) secondary to hyperventilation is generally accepted to play a major role in the decrease of cerebral tissue oxygen saturation (SctO2 ), it remains unclear if the associated systemic hemodynamic changes are also accountable. METHODS: Twenty-six patients (American Society of Anesthesiologists I-II) undergoing nonneurosurgical procedures were anesthetized with either propofol-remifentanil (n = 13) or sevoflurane (n = 13). During a stable intraoperative period, ventilation was adjusted stepwise from hypoventilation to hyperventilation to achieve a progressive change in end-tidal CO2 (ETCO2 ) from 55 to 25 mmHg. Minute ventilation, SctO2 , ETCO2 , mean arterial pressure (MAP), and cardiac output (CO) were recorded. RESULTS: Hyperventilation led to a SctO2 decrease from 78 ± 4% to 69 ± 5% (Δ = -9 ± 4%, P < 0.001) in the propofol-remifentanil group and from 81 ± 5% to 71 ± 7% (Δ = -10 ± 3%, P < 0.001) in the sevoflurane group. The decreases in SctO2 were not statistically different between these two groups (P = 0.5). SctO2 correlated significantly with ETCO2 in both groups (P < 0.001). SctO2 also correlated significantly with MAP (P < 0.001) and CO (P < 0.001) during propofol-remifentanil, but not sevoflurane (P = 0.4 and 0.5), anesthesia. CONCLUSION: The main mechanism responsible for the hyperventilation-induced decrease in SctO2 is hypocapnia during both propofol-remifentanil and sevoflurane anesthesia. Hyperventilation-associated increase in MAP and decrease in CO during propofol-remifentanil, but not sevoflurane, anesthesia may also contribute to the decrease in SctO2 but to a much smaller degree.

Changes in cerebral tissue oxygen saturation during anaesthetic-induced hypotension: an interpretation based on neurovascular coupling and cerebral autoregulation.

There is currently no consensus regarding how to intervene in anaesthetic-induced hypotension. Whether or not the balance between cerebral oxygen supply and demand is maintained lacks adequate elucidation. It is thus intriguing to explore how cerebral tissue oxygen saturation is affected by anaesthetic-induced hypotension. Thirty-three patients scheduled for elective non-neurosurgical procedures were included in this study. Physiological measurements were performed immediately before induction with propofol and fentanyl and after tracheal intubation. Mean (SD) Bispectral index decreased from 84.3 (9.3) to 24.4 (8.0) (p<0.001). Mean arterial pressure decreased from 84.4 (10.6) mmHg to 53.6 (11.4) mmHg (p<0.001). However, cerebral tissue oxygen saturation remained stable (67.0 (9.4) % vs 67.5 (7.8) %, p=0.6). These results imply that the fine balance between cerebral oxygen supply and demand is not disrupted by anaesthetic-induced hypotension. An interpretation based on neurovascular coupling and cerebral autoregulation is proposed.

Impact of phenylephrine administration on cerebral tissue oxygen saturation and blood volume is modulated by carbon dioxide in anaesthetized patients.

BACKGROUND: Multiple studies have shown that cerebral tissue oxygen saturation (Sct(O(2))) is decreased after phenylephrine treatment. We hypothesized that the negative impact of phenylephrine administration on Sct(O(2)) is affected by arterial blood carbon dioxide partial pressure (Pa(CO(2))) because CO(2) is a powerful modulator of cerebrovascular tone. METHODS: In 14 anaesthetized healthy patients, i.v. phenylephrine bolus was administered to increase the mean arterial pressure ~20-30% during hypocapnia, normocapnia, and hypercapnia. Sct(O(2)) and cerebral blood volume (CBV) were measured using frequency domain near-infrared spectroscopy, a quantitative technology. Data collection occurred before and after each treatment. RESULTS: Phenylephrine caused a significant decrease in Sct(O(2)) during hypocapnia [ΔSct(O(2)) =-3.4 (1.5)%, P<0.001], normocapnia [ΔSct(O(2)) =-2.4 (1.5)%, P<0.001], and hypercapnia [ΔSct(O(2)) =-1.4 (1.5)%, P<0.01]. Decreases in Sct(O(2)) were significantly different between hypocapnia, normocapnia, and hypercapnia (P<0.001). Phenylephrine also caused a significant decrease in CBV during hypocapnia (P<0.01), but not during normocapnia or hypercapnia. CONCLUSION: The negative impact of phenylephrine treatment on Sct(O(2)) and CBV is intensified during hypocapnia while blunted during hypercapnia.

Perfusion mapping using computed tomography allows accurate prediction of cerebral infarction in experimental brain ischemia.

BACKGROUND AND PURPOSE: We have developed a dynamic CT method to measure absolute cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). In this study we evaluated the ability of CT-derived functional maps to detect infarction in a rabbit model of focal cerebral ischemia. METHODS: Sequential dynamic CT studies were performed at 2 different slices in 5 control rabbits and another 8 after induction of focal cerebral ischemia. The size of critically ischemic tissue was correlated to size of infarction measured by postmortem 2,3,5-triphenyltetrazolium chloride staining. In the control rabbits, short-term variability of the parameters was assessed by ANOVA analysis. RESULTS: In 7 of 8 animals of the ischemia group, cerebral infarction was visible on 2,3, 5-triphenyltetrazolium chloride staining, constituting 16.7+/-10.6% of the ipsilateral hemisphere. Good agreement of CBF functional maps with tissue specimens was found with respect to size and location of infarction. Best prediction of infarction was found for thresholds of CBF <10 mL/100 g per minute (mean size, 17.5+/-13.4%; r=0.95) and MTT >6 seconds (mean size, 15.6+/-13.5%; r=0.85), with regression slopes close to unity. CBV maps were less predictive of occurrence of infarction, especially in cases of small infarction. The short-term variability of CBF, CBV, and MTT in the control group was 10.9%, 15.2%, and 19.9%, respectively. CONCLUSIONS: Functional CT measurements of absolute CBF and MTT early after onset of ischemia allow prediction of the size and location of cerebral infarction with good accuracy.

Enflurane and halothane in status asthmaticus.

A patient with status asthmaticus deteriorated while receiving conventional therapy including mechanical ventilation. She failed to respond to the inhalation of enflurane but had a beneficial response to halothane. Her subsequent course was complicated by a prolonged metabolic encephalopathy which was associated with an elevated plasma bromide level from the metabolism of halothane.

Glutamate stimulates ascorbate transport by astrocytes.

The concentrations of glutamate and ascorbate in brain extracellular fluid increase following seizure activity, trauma and ischemia. Extracellular ascorbate concentration also rises following intracerebral glutamate injection. We hypothesized that glutamate triggers the release of ascorbate from astrocytes. We observed in primary cultures of rat cerebral astrocytes that glutamate increased ascorbate efflux significantly within 30 min. The half-maximal effective concentration of glutamate was 180+/-30 microM. Glutamate-stimulated efflux of ascorbate was attenuated by hypertonic media. 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid inhibited both Na(+)-dependent glutamate uptake and ascorbate efflux. Two other inhibitors of volume-sensitive organic anion channels (1, 9-dideoxyforskolin and 5-nitro-2-(3-phenylpropylamino) benzoic acid) did not slow glutamate uptake but prevented stimulation of ascorbate efflux. Glutamate also stimulated the uptake of ascorbate by ascorbate-depleted astrocytes. In contrast, glutamate uptake was not affected by intracellular ascorbate, thus ruling out a putative glutamate-ascorbate heteroexchange mechanism. These results are consistent with activation by glutamate of ascorbate-permeant channels in astrocytes.

A CT method to measure hemodynamics in brain tumors: validation and application of cerebral blood flow maps.

BACKGROUND AND PURPOSE: CT is an imaging technique that is routinely used for evaluating brain tumors. Nonetheless, imaging often cannot show the distinction between radiation necrosis and neoplastic growth among patients with recurrent symptoms after radiation therapy. In such cases, a diagnostic tool that provides perfusion measurements with high anatomic detail would show the separation between necrotic areas, which are characterized by low perfusion, from neoplastic areas, which are characterized by elevated CBF. We attempted to validate a dynamic contrast-enhanced CT method for the measurement of regional CBF in brain tumors, and to apply this method by creating CBF maps. METHODS: We studied nine New Zealand White rabbits with implanted brain tumors. We obtained dynamic CT measurements of CBF, cerebral blood volume (CBV), and permeability surface (PS) from the tumor, peritumor, and contralateral normal tissue regions. In all nine rabbits (two studies per rabbit), we compared CT-derived CBF values with those simultaneously obtained by the standard of reference ex vivo microsphere technique. Using CT, we examined three rabbits to assess the variability of repeated CBF and CBV measurements; we examined the other six to evaluate regional CBF reactivity to arterial carbon dioxide tensions. Finally, CT CBF maps were obtained from a rabbit with a brain tumor during normocapnia and hypocapnia. RESULTS: We found a significant linear correlation (r = 0.847) between the regional CT-and microsphere-derived CBF values, with a slope not significantly different from unity (0.99+/-0.03, P>.01). The mean difference between regional CBF measurements obtained using both methods did not significantly deviate from zero (P>.10). During normocapnia, tumor had significantly higher CBF, CBV, and PS values (P<.05) than did peritumor and normal tissues. The variability in CT-derived CBF and CBV measurements in the repeated studies was 13% and 7%, respectively. CT revealed no significantly different CBF CO2 reactivity from that determined by the microsphere method (P>.10). The CBF map of tumor regions during normocapnia showed much higher flow than normal regions manifested, and this difference was reduced on the hypocapnia CBF map. CONCLUSION: The dynamic CT method presented herein provides absolute CBF measurements in brain tumors that are accurate and precise. Preliminary CBF maps derived with this method demonstrate their potential for depicting areas of different blood flow within tumors and surrounding tissue, indicating its possible use in the clinical setting.