Pre-operative biomarkers and imaging tests as predictors of post-operative delirium in non-cardiac surgical patients: a systematic review.

BACKGROUND: Post-operative delirium (POD) is a common post-operative complication in elderly individuals and imposes a significant health and financial burden. Identifying predictive biomarkers may help understand the pathophysiology of POD. Our objective is to summarize the evidence of pre-operative biomarkers and imaging tests to predict POD in patients undergoing non-cardiac surgery. METHODS: A systematic search of English language articles in MEDLINE, EMBASE, Cochrane Database, PsychINFO, PubMed and ClinicalTrials. Gov up to January 2018 was performed. Studies that used biomarkers or imaging tests to predict POD and a validated POD assessment tool were included. Animal studies, paediatric, cardiac and intracranial surgery were excluded. Risk of bias was assessed using the Quality In Prognosis Study tool. RESULTS: Thirty-four prospective cohort studies involving 4424 patients were included. Nineteen studies described serum tests [Interleukin-6, Insulin-like Growth Factor 1, C-Reactive Protein (CRP), cholinesterases, apolipoprotein-E genotype, leptin, hypovitaminosis, hypoalbuminaemia, gamma-amino butyric acid], 10 described cerebral-spinal fluid tests (monoamine precursor, melatonin, acute phase proteins, S100B and neurofibrillary tangles), and 5 described imaging tests. Two studies had high risk of bias due to unclear outcome measurement and study participation. CRP was significantly associated with POD in 5 studies. Other biomarkers were either examined by only a single study or two or more studies with conflicting results. CONCLUSION: CRP is the most promising biomarker associated with POD. However, we are still in the early stages in identifying biomarkers and imaging tests that may further understanding of the pathophysiology of POD.

The effects of adding local infiltration analgesia of the knee to a multimodal pain protocol for total arthroplasty: A matched pair retrospective study.

Background: We hypothesize that the addition of local infiltration analgesia (LIA) to a multimodal pain protocol will reduce the total amount of opioids consumed for acute pain control post total knee arthrolplasty (TKA). Methods: This study was a retrospective, matched pair study including patients who had primary TKA. All patients included in the analysis had preoperative oral celecoxib and acetaminophen, had single-dose spinal anesthetic with intrathecal morphine, and had intravenous patient-controlled analgesia with an opioid agent in addition to gabapentin and celecoxib in the first 48 h. Patients whose charts were excluded from the study had revision TKA, received opioid therapy prior to the surgery, were classified as American Society of Anesthesiology (ASA) IV, and had general anesthesia. Fifty patients who underwent TKA and had LIA were matched for age, body mass index (BMI), and gender with patients who did not receive LIA. The primary outcome measures were total doses of opioids consumed post TKA. Results: Patients receiving LIA consumed on average significantly less intravenous (IV) morphine equivalents than patients not receiving LIA, with a mean difference (±SD) of 88.9 ± 15.6 mg IV morphine equivalents. Furthermore, pain control was better in the LIA group. The incidences of nausea and vomiting, pruritis, and excessive sedation were higher in the non-LIA group compared to the LIA group. There was no difference in the hospital length of stay between both groups. Conclusions: The addition of LIA to our multimodal pain protocol for TKA was associated with a reduction in total opioid consumption.

Contexte: Nous émettons l'hypothèse que l'ajout d'une analgésie locale par infiltration à un protocole de prise en charge de la douleur multimodal réduira la quantité totale d'opioïdes consommée pour maitriser la douleur aigue après une arthroplastie totale du genou (ATG).Méthodes: Cette étude était une étude rétrospective appariée ont les participants étaient des patients ayant subi une ATG primaire. Tous les patients inclus dans l'analyse s'étaient vus administrer du célécoxib et de l'acétaminophène en période préopératoire, une dose unique d'anasthésiant rachidien sous forme de morphine intrathécale et un analgésique intraveineux contrôlé par le patient comprenant un agent opioïde, en plus de la gabapentine et de l'acélécoxib au cours des premières 48 heures. Les patients dont les dossiers ont été exclus de l'étude avaient subi une ATG de reprise, avaient consommé des opioïdes avant la chirurgie, étaient classés ASA IV et avaient subi une anesthésie générale. Cinquante patients ayant subi une ATG et une analgésie locale par infiltration ont été appariés selon l'âge, l'IMC et le genre avec des patients qui n'avaient pas reçu d'analgésie locale par infiltration. Les résultats primaires ont été mesurés par les doses totales d'opioïdes consommées après l'ATG.Résultats: En moyenne, les patients ayant reçu une analgésie locale par infiltration ont consommé significativement moins d'équivalents morphine IV que les patients qui n'avaient pas reçu d'analgésie locale par infiltration, avec une différence moyenne (± É.-T.) de 88,9 ± 15,6 mg d'équivalents morphine IV. De plus, la douleur était mieux maitrisée dans le groupe ayant reçu une analgésie locale par infiltration. L'incidence des vomissments, du prurit et de la sédation excessive était plus élevée dans le groupe n'ayant pas reçu d'analgésie locale par infiltration que dans le groupe ayant reçu une analgésie locale par infiltration. Il n'y avait pas de différence entre les deux groupes en ce qui concerne la durée du séjour à l'hôpital.Conclusions: L'ajout d'une analgésie locale par infiltration à notre protocole douleur multimodal pour l'arthroplastie totale du genou était associé à une réduction dans la consommation totale d'opioïdes.

Tranexamic acid administration to older patients undergoing primary total hip arthroplasty conserves hemoglobin and reduces blood loss.

BACKGROUND: Tranexamic acid effects in older people are difficult to predict. This study investigated the following research questions: 1) Is tranexamic acid effective in older patients undergoing primary total hip arthroplasty (THA)? and 2) Is there a difference in the effect of tranexamic acid between younger and older patients? METHODS: This was a 2-phase retrospective matched-pair study of patients who underwent THA in 2007-2013. All procedures were performed by surgeons with at least 10 years' experience as senior consultant. In the first phase, 58 patients aged 65 years or more who received tranexamic acid were matched 1:1 with patients who did not receive tranexamic acid for age, sex, American Society of Anesthesiologists (ASA) classification and body mass index. In the second phase, 58 patients aged 65 years or more who received tranexamic acid were matched 1:1 with patients less than 65 years of age who received tranexamic acid for sex, ASA classification and body mass index. The primary outcome measures were percent maximum decrease in hemoglobin level and estimated blood loss after surgery. RESULTS: In the first phase, patients who received tranexamic acid conserved postoperative hemoglobin by a mean of 10.26 g/L (standard deviation [SD] 9.89 g/L) compared to the control group (p < 0.001). The mean difference in the estimated perioperative blood loss between the 2 groups was 410 mL (SD 376 mL) (p < 0.001), which indicated less bleeding in the treatment group. In the second phase, there was no difference between the younger (mean age 55.1 [SD 7.28] yr) and older (mean age 75.6 [SD 6.35] yr) groups in mean lowest postoperative hemoglobin level or percent decrease in hemoglobin level. CONCLUSION: Tranexamic acid reduced the postoperative decrease in hemoglobin level and blood loss in older patients. Moreover, the significant hemoglobin-sparing effect of tranexamic acid in older patients was similar to that observed in younger patients.

CONTEXTE: Les effets de l'acide tranexamique sont difficiles à prévoir chez les personnes âgées. Avec cette étude, nous avons voulu répondre aux 2 questions suivantes : 1) L'acide tranexamique est-il efficace chez les patients âgés soumis à une intervention chirurgicale primaire pour prothèse totale de la hanche (PTH)?, et 2) L'acide tranexamique produit-il un effet différent selon que les patients sont jeunes ou âgés? MÉTHODES: Cette étude rétrospective en 2 phases sur des paires appariées a regroupé des patients soumis à une intervention pour PTH entre 2007 et 2013. Toutes les interventions ont été effectuées par des chirurgiens détenant au moins 10 ans d'expérience à titre de consultants principaux. Au cours de la première phase, 58 patients de 65 ans ou plus ayant reçu de l'acide tranexamique ont été assortis (rapport 1:1), selon l'âge, le sexe, la classification ASA (American Society of Anesthesiologists) et l'indice de masse corporelle, à des patients n'en ayant pas reçu. Au cours de la deuxième phase, 58 patients de 65 ans ou plus ayant reçu de l'acide tranexamique ont été assortis (rapport 1:1), selon le sexe, la classification ASA et l'indice de masse corporelle, à des patients de moins de 65 ans ayant aussi reçu de l'acide tranexamique. Les paramètres principaux étaient la diminution maximale en pourcentage du taux d'hémoglobine et la perte sanguine estimée après l'intervention chirurgicale. RÉSULTATS: Pour la première phase, les patients qui ont reçu l'acide tranexamique ont maintenu une hémoglobine postopératoire moyenne à 10,26 g/L (écart-type [É.-T.] 9,89 g/L) comparativement au groupe témoin (p < 0,001). La différence moyenne entre les 2 groupes pour ce qui est des pertes sanguines periopératoires a été de 410 mL (É.-T. 376 mL) (p < 0,001), indiquant de ce fait une perte sanguine moindre dans le groupe traité. Pour la deuxième phase, on n'a noté aucune différence entre le groupe plus jeune (âge moyen 55,1 ans [É.-T. 7,28 ans]) et le groupe plus âgé (âge moyen 75,6 ans [É.-T. 6,35 ans]) pour ce qui est du taux d'hémoglobine postopératoire moyen le plus bas ou le pourcentage de baisse du taux d'hémoglobine. CONCLUSION: L'acide tranexamique a permis d'atténuer la baisse postopératoire de l'hémoglobine et les pertes sanguines chez les patients âgés. De plus, l'effet significatif de l'acide tranexamique sur le maintien de l'hémoglobine chez les patients âgés a été similaire à ce qui s'observe chez les patients plus jeunes.

Continuous infraclavicular brachial plexus blockade: effect on survival of replanted digits.

In replantation surgery, the use of continuous brachial plexus blockade (CBPB) is popular as it improves postoperative analgesia and vascular flow. The aim of our study was to determine whether CBPB may affect the odds of survivability of replanted digit(s). A four-year retrospective chart review was performed and various parameters affecting replant survival were examined. Outcome was recorded as successful if the transplanted digit(s) survived six months after discharge. All the independent variables were forced into a regression model without using a specific variable selection algorithm. The data for 146 patients was obtained from our chart review. The success rate of replanted digits in the patients reviewed was 65.8%. The logistic regression model showed a relation between the number of digits injured and replanted digit(s) survival. Our study showed that CBPB has no effect on the survivability of the replanted digit(s) till six months after hospital discharge.

Spectral features of electroencephalogram in characterizing various brain states under anesthesia.

The administration of the anesthetic agents is known to alter the electroencephalogram (EEG) signal significantly with the brain being their primary target. In this study, we analyzed the EEG recorded from six ASA I/II patients undergoing a 1-2 hour surgery. The EEG was collected before and during induction, maintenance and recovery of anesthesia using the 10/20 lead-system. A combination of fentanyl and propofol (± rocuronium) was used for induction and a Sevoflurane in air/O(2) mixture was administered through an endotracheal tube to achieve the steady minimum alveolar concentration (MAC). This study showed that 0 to 4 Hz signal power was most sensitive to the changes associated with induction of anesthesia whereas the 4 to 12 Hz power was important in classifying states during maintenance of anesthesia. Anesthesia also promoted heightened phase coherence in 8 to 16 Hz and 16 to 30 Hz ranges during maintenance and induction of anesthesia, respectively. Additionally, strong cross-frequency coupling between 7 to 20 Hz and 10 to 40 Hz was observed during anesthesia suggesting alteration of neural coding.

Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial.

BACKGROUND: Topical application of tranexamic acid to bleeding wound surfaces reduces blood loss in patients undergoing some major surgeries, without systemic complications. The objective of the present trial was to assess the efficacy and safety of the topical application of tranexamic acid on postoperative blood loss in patients undergoing primary unilateral total knee arthroplasty with cement. METHODS: In a prospective, double-blind, placebo-controlled trial, 124 patients were randomized to receive 1.5 or 3.0 g of tranexamic acid in 100 mL of normal saline solution or an equivalent volume of placebo (normal saline solution) applied into the joint for five minutes at the end of surgery. The primary outcome was blood loss calculated from the difference between the preoperative hemoglobin level and the corresponding lowest postoperative value or hemoglobin level prior to transfusion. The safety outcomes included Doppler ultrasound in all patients and measurement of plasma levels of tranexamic acid one hour after release of the tourniquet. RESULTS: Twenty-five patients were withdrawn for various reasons; therefore, ninety-nine patients were included in the intention-to-treat analysis. The postoperative blood loss was reduced in the 1.5 and 3-g tranexamic acid groups (1295 mL [95% confidence interval, 1167 to 1422 mL] and 1208 mL [95% confidence interval, 1078 to 1339 mL], respectively) in comparison with the placebo group (1610 mL [95% confidence interval, 1480 to 1738 mL]) (p < 0.017). The postoperative hemoglobin levels were higher in the 1.5 and 3.0-g tranexamic acid groups (10.0 g/dL [95% confidence interval, 9.5 to 10.4 g/dL] and 10.1 g/dL [95% confidence interval, 9.8 to 10.5 g/dL], respectively) in comparison with the placebo group (8.6 g/dL [95% confidence interval, 8.2 to 9 g/dL]) (p < 0.017). With the numbers studied, there was no difference in the rates of deep-vein thrombosis or pulmonary embolism between the three groups. Minimal systemic absorption of tranexamic acid was observed. CONCLUSIONS: At the conclusion of a total knee arthroplasty with cement, topical application of tranexamic acid directly into the surgical wound reduced postoperative bleeding by 20% to 25%, or 300 to 400 mL, resulting in 16% to 17% higher postoperative hemoglobin levels compared with placebo, with no clinically important increase in complications being identified in the treatment groups.

Improved esophageal patency when inserting the ProSeal laryngeal mask airway with an Eschmann tracheal tube introducer.

PURPOSE: We hypothesized that a more accurate alignment of the tip of the drain tube with the upper esophageal opening would be achieved in adult patients, as confirmed by fibreoptic bronchoscopy, by placing the ProSeal laryngeal mask airway (PLMA) by means of guiding it over an Eschmann tracheal tube introducer, commonly know as a gum elastic bougie (GEB), that was previously inserted into the esophagus, rather than by placing the PLMA with a curved metal introducer (IT). METHODS: Seventy-five adult elective surgery patients, whose airway management involved a PLMA, were randomly allocated to either the GEB- or IT-guided techniques. After inserting the PLMA, alignment of the tip of the drain tube relative to the esophageal opening was verified by a fibrescope introduced through the drain tube. Placing the fibrescope through the PLMA identified the glottic structures. The primary endpoint indicating the proper alignment of the tip of the drain tube of the PLMA with the upper esophageal opening was the ability to pass the fibrescope into the esophagus through the drain tube by a distance >35 cm without obstruction and the ability to simultaneously visualize the esophageal mucosa. RESULTS: The overall success rates of PLMA insertion were similar in the GEB and IT groups. However, the mean airway insertion times were longer with the GEB than with the IT-PLMA. The GEB group achieved proper alignment of the drain tube and the upper esophageal opening more frequently than the IT group (97% confidence interval (CI(95)) 91.5-100% vs 81% CI(95) 68.5-93.5% of subjects, respectively; P = 0.027). When the GEB was used to place the PLMA, the patients' vocal cords were visualized more frequently than when the IT technique was used (100% vs 73% CI(95) 58.9-87.1% of subjects, respectively; P = 0.003). CONCLUSION: Fibreoptic bronchoscopy confirmed that GEB is superior to the IT technique in ensuring precise alignment of the tip of the drain tube of the PLMA with the upper esophageal opening. Accurate positioning may better preserve gastroesophageal drainage function of the PLMA.

Minimum effective volume of local anesthetic for ultrasound-guided supraclavicular brachial plexus block.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the minimum effective anesthetic volume required to produce an effective supraclavicular block for surgical anesthesia using an ultrasound (US)-guided technique. METHODS: Twenty-one adults undergoing elective upper limb surgery received a US-guided supraclavicular block. The initial volume of local anesthetic (LA; 50:50 mixture of lidocaine 2% and bupivacaine 0.5% with epinephrine) injected was 30 mL, which was subsequently varied by 5 mL for each consecutive patient according to the response of the previous patient. The minimum effective anesthetic volume in 50% of patients was determined using the Dixon and Massey up-and-down method. The effective volume in 95% of patients (ED95) was calculated using probit transformation and logistic regression. RESULTS: The minimum effective anesthetic volume in 50% and calculated effective volume in 95% of patients were 23 mL (95% confidence interval, 13-39 mL) and 42 mL (95% confidence interval, 19-65 mL), respectively. Seven patients received supplemental LA, with no patient requiring a general anesthetic. CONCLUSION: In this study, the minimum volume required for US-guided supraclavicular block in 50% of patients was 23 mL, and in 95% of patients was 42 mL. Under the present study conditions, the calculated volume of LA required for US-guided supraclavicular block does not seem to differ from the conventionally recommended volume required for supraclavicular blocks using non-US-based nerve localization techniques.

Tranexamic Acid reduces perioperative blood loss in adult patients having spinal fusion surgery.

BACKGROUND: Spinal reconstructive surgery in adults can be associated with significant blood loss, often requiring allogeneic blood transfusion. The objective of this randomized, prospective, double-blind, multicenter study was to evaluate the efficacy of tranexamic acid (TXA) in reducing perioperative blood loss and transfusion in adult patients having elective posterior thoracic/lumbar instrumented spinal fusion surgery. METHODS: One hundred fifty-one adult patients were randomized to receive either a bolus of 10 mg/kg IV of TXA after induction followed by a maintenance infusion of 1 mg/kg/hr of TXA, or an equivalent volume of placebo (normal saline). The primary outcome was the total perioperative estimated and calculated blood loss intraoperatively and 24 h postoperatively. Secondary outcomes were incidence of allogeneic blood exposure, and duration of hospital stay. RESULTS: Four patients were withdrawn for identifiable surgical bleeding, therefore 147 patients were included in the analysis. The total estimated and calculated perioperative blood loss was approximately 25% and 30% lower in patients given TXA versus placebo (1592 +/- 1315 mL vs 2138 +/- 1607 mL, P = 0.026; 3079 +/- 2558 vs 4363 +/- 3030, P = 0.017), respectively. There was no difference in the amounts of blood products transfused, and length of stay between the two groups. TXA, surgical duration, and number of vertebrae fused were independent factors related to perioperative blood loss. Predictors for the need for allogeneic red blood cell transfusion were ASA classification, surgical duration and number of levels fused. CONCLUSIONS: TXA significantly reduced the estimated and calculated total amount of perioperative blood loss in adult patients having elective posterior thoracic/lumbar instrumented spinal fusion surgery.

Management of the airway in patients undergoing cervical spine surgery.

The perioperative management of the airway in patients with cervical spine disease requires careful consideration. In an observational prospective cohort study, we assessed the preoperative factors that may have influenced the anesthesiologists' choice for the technique of intubation and the incidence of postoperative airway complications. We recorded information from 327 patients: mean (+/-SD) age 51+/-15 year, 138 females and 189 males, for anterior surgical approach (n=195) and posterior (n=132). The technique of intubation used was awake fiberoptic bronchoscopy (FOB) in 39% (n=128), asleep FOB 32% (n=103), asleep laryngoscopy 22% (n=72), and other asleep 7% (n=24). Awake FOB was predominately chosen for intubating patients with myelopathy (45%), unstable/fractured spine (73%), and spinal stenosis (55%) but patients with radiculopathy had more asleep FOB (49%) (P<0.001). There was no association between method of intubation and postoperative airway complications. Acute postoperative airway obstruction occurred in 4 (1.2%) patients requiring reintubation. The technique of management of the airway for cervical spine surgery varied considerably among the anesthesiologists, although the choice was not associated with postoperative airway complications.

Myelination of congenitally dysmyelinated spinal cord axons by adult neural precursor cells results in formation of nodes of Ranvier and improved axonal conduction.

Emerging evidence suggests that cell-based remyelination strategies may be a feasible therapeutic approach for CNS diseases characterized by myelin deficiency as a result of trauma, congenital anomalies, or diseases. Although experimental demyelination models targeted at the transient elimination of oligodendrocytes have suggested that transplantation-based remyelination can partially restore axonal molecular structure and function, it is not clear whether such therapeutic approaches can be used to achieve functional remyelination in models associated with long-term, irreversible myelin deficiency. In this study, we transplanted adult neural precursor cells (aNPCs) from the brain of adult transgenic mice into the spinal cords of adult Shiverer (shi/shi) mice, which lack compact CNS myelin. Six weeks after transplantation, the transplanted aNPCs expressed oligodendrocyte markers, including MBP, migrated extensively along the white matter tracts of the spinal cord, and formed compact myelin. Conventional and three-dimensional confocal and electron microscopy revealed axonal ensheathment, establishment of paranodal junctional complexes leading to de novo formation of nodes of Ranvier, and partial reconstruction of the juxtaparanodal and paranodal molecular regions of axons based on Kv1.2 and Caspr (contactin-associated protein) expression by the transplanted aNPCs. Electrophysiological recordings revealed improved axonal conduction along the transplanted segments of spinal cords. We conclude that myelination of congenitally dysmyelinated adult CNS axons by grafted aNPCs results in the formation of compact myelin, reconstruction of nodes of Ranvier, and enhanced axonal conduction. These data suggest the therapeutic potential of aNPCs to promote functionally significant myelination in CNS disorders characterized by longstanding myelin deficiency.

Venous air embolism during awake craniotomy in a supine patient.

PURPOSE: To report a non-fatal case of intraoperative venous air embolism (VAE) during an awake craniotomy. VAE presented with unusual clinical features. CLINICAL FEATURES: VAE during an awake craniotomy has not been reported frequently. The patient we describe presented with persistent coughing followed by tachypnea, hypoxia and reduction in end-tidal CO(2) during dural opening while undergoing an awake craniotomy in the supine position. Cardiovascular variables were stable during the episode except for transient hypertension. Having ruled out airway obstruction and low cardiac output, we concluded that air embolism was the cause. The patient responded immediately to the standard treatment of air embolism and recovered without any complication. CONCLUSION: This case illustrates a VAE during an awake craniotomy and emphasizes the importance of early diagnosis in the management.