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11. Frerk C, Mitchell VS, McNarry AF, et al. Difficult Airway Society 2015 guidelines for management of unanticipated difficult intubation in adults. Br J Anaesth 2015; 115: 827–48 12. Caldiroli D, Cortellazzi P. A new difficult airway management algorithm based upon the El Ganzouri Risk Index and GlideScope(R) videolaryngoscope: a new look for intubation? Minerva Anestesiol 2011; 77: 1011–7 13. Russo SG, Weiss M, Eich C. Video laryngoscopy ole! Time to say good bye to direct and flexible intubation? Anaesthesist 2012; 61: 1017–26 14. Lundstrom LH, Moller AM, Rosenstock C, et al. A documented previous difficult tracheal intubation as a prognostic test for a subsequent difficult tracheal intubation in adults. Anaesthesia 2009; 64: 1081–8 15. Greenland KB, Segal R, Acott C, Edwards MJ, Teoh WH, Bradley WP. Observations on the assessment and optimal

16.

17.

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use of videolaryngoscopes. Anaesth Intensive Care 2012; 40: 622–30 Greenland KB, Bradley WPL, Teoh WH, Acott C, Segal R. Use of Cormack and Lehane grading with videolaryngoscopy-Reply. Anaesth Intensive Care 2013; 41: 123–4 Teoh WH, Kristensen MS. Ultrasonographic identification of the cricothyroid membrane. Anaesthesia 2014; 69: 649–50 Kristensen MS, Teoh WH, Baker PA. Percutaneous emergency airway access; prevention, preparation, technique and training. Br J Anaesth 2015; 114: 357–61 Kristensen MS, Teoh WH, Rudolph SS, et al. Structured approach to ultrasound-guided identification of the cricothyroid membrane: a randomized comparison with the palpation method in the morbidly obese. Br J Anaesth 2015; 114: 1003–4

British Journal of Anaesthesia 117 (1): 3–5 (2016) doi:10.1093/bja/aew147

Skeletal muscle and plasma concentrations of cefazolin P. C. Jutte, J. J. W. Ploegmakers and S. K. Bulstra* Department of Orthopedic Surgery, University Medical Center Groningen (UMCG), Hanzeplein 1, Groningen 9700 RB, The Netherlands *Corresponding author. E-mail: [email protected]

Surgical site infections are serious complications of surgery, particularly after orthopaedic surgery, where biomaterial infection has serious implications for the patient and poses a significant financial burden on society. Antibiotic prophylaxis is an important component of strategies to prevent surgical site infection, and although it has become part of routine practice before and during many surgical procedures, it has been insufficiently investigated. The study published by Himebauch and colleagues1 in this issue of the BJA is thus a very welcome and much needed addition to the literature on this topic. In their well written article the authors report skeletal muscle and plasma concentrations of Cefazolin during complex pediatric spinal surgery. These muscle concentrations are important, as insufficient concentrations may very well result in possible surgical site infections (SSI). Although data on the serum concentrations are well known, there are not many studies showing concentrations in the tissues surrounding the implant, which is where adequate antibiotic concentrations are necessary to prevent biofilm formation. The use of microdialysis in this study is innovative and safe and may represent an important adjunct in the quest to gain insight into the actual local tissue antibiotic concentrations. The administration of prophylactic antibiotics is part of routine practice. Most commonly when permanently implanted biomaterial are placed, a cephalosporin is administered perioperatively. In large register-based studies of orthopaedic joint replacements, antibiotic prophylaxis has been associated with significantly reduced infection rates. Unfortunately the timing of administration before surgery, dosage and the administration of repeat perioperative dosage are debatable subjects, on which this article can cast some light. From the current article we can learn that in this vulnerable group of children with scoliosis,

especially those with neuromuscular abnormalities, the concentrations are too low at the time of the incision. Also, given the duration of these operations, the local concentration of antibiotics decreases to an undesired low concentration during surgery. The measurements in table 3 show that the protection, especially against gram negative bacteria, is too low. Inadequate concentrations of antibiotics are not helpful in the prevention of biofilm formation, and may even induce bacterial resistance to antibiotics that are usually optimal for prophylactic treatment. It is common knowledge that implanted biomaterials, such as those used in joint replacement are prone to infection. During the proceedings of the international consensus meeting on periprosthetic joint infection held in 2013, with virtually all the representatives of orthopaedic surgery present, consensus was reached on many subjects.2 The efficacy of antimicrobial prophylaxis in preventing infections is a well-established,3 and preoperative i.v. antibiotic prophylaxis is regarded as the corner stone for the prevention of infection in all patients undergoing biomaterial implantation. In operations that last for more than one h, an increasing infection rate is found even in the absence of implantation materials. Therefore more rigid treatment regimens for longer operations, and for high-risk patients, such as patients with diabetes, severe obesity and other risk factors, are introduced. It is also important that preoperative measurements for reduction of the risk for an infection, such as decolonization for MRSA and/or other MSSA bacteria in patients, are introduced and implemented. After the insertion of a prosthesis into the human body a race between bacteria and host cells for the surface of the implant begins. If bacteria get the chance they will develop a so-called biofilm around the implant, a self-produced extracellular polymeric

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substance (slime layer). This biofilm protects the bacteria from the outside world, so that the immunological defense system if the patient has difficulty in sensing and attacking the bacteria inside the biofilm. Administered antibiotics may also have limited penetration into the surface of the biofilm, and frequently cannot reach the bacteria that are inside the biofilm. Therefore if an infection occurs in the presence of a biomaterial, such as a total hip prosthesis, the only way to eradicate this problem is the removal of the implant. It is clear from these data that antibiotic prophylaxis is not only needed at the start of the operation, but adequate concentrations of antibiotics should be present during the whole operation.3 A first or second generation cephalosporin (such as cefalozin or cefuroxime) should be administered for routine perioperative surgical prophylaxis. Isoxazolyl penicillin is used as an appropriate alternative. In patients with non-anaphylactic penicillin allergy, second generation cephalosporines are advised and in general can be used safely. Penicillin skin testing may be helpful in certain situations to clarify whether a patient has a true penicillin allergy. If a patient has a known anaphylactic penicillin allergy, vancomycin or clindamycin should be administered. These antibiotics are chosen based on the coverage of grampositive organisms and clinically important gram negative bacilli and anaerobic gram positive organisms. They also have an excellent distribution profile in bone, synovium, muscle and haematomas. The optimal prophylactic antibiotic regimen should preferably contain bactericidal antibiotics. The half-life of the chosen agent should be sufficient to provide cover for the important parts of the operation - at least the first two h of the operation, covering the time from incision to closure of the wound.4–10 There is ongoing discussion on the required duration of adequate concentrations of antibiotics after the operation. Several researchers have found that in contrast to earlier regimes, a 24 h regimen was not associated with an increase in the infection rate when compared with a seven day or 48 h regimen.13 Studies are now addressing an even shorter duration of an adequate concentration of antibiotics after an operation. The timing of administration before operation is critical. Optimal timing before surgery appears to be 60–30 min before the surgery.13 When using different agents for prophylaxis, timing of administration should be altered, to match the pharmacokinetics and dynamics of the agent. For vancomycin or fluoroquinolones for example, administration two h before surgery is probably better able to ensure an optimal concentration at surgical incision. In patients where a tourniquet is used, then administration of the antibiotics at least ten min before inflation of the tourniquet, or directly after the release of the tourniquet, seem to be the optimal moments to ensure adequate concentrations in bone and fat.14 For longer duration procedures, an additional dose of antibiotics should be administered after two half-lives have elapsed since the administration of the first dose of the prophylactic agent.15–17 Adequate antibiotic concentrations were found in bone after five min, and in fat after 10 min after i.v. administration of a repeat dose.14 Repeat dosing of antibiotics according to the guidelines should also be considered if there is a large volume of blood loss (>2000 ml) or administration of more than 2000 ml of fluid resuscitation. Because these are independent variables, re-doing should be considered as soon as one of the mentioned conditions is met. For future research this means that not only the right timing (i.e. 30–60 min before the surgical incision) is required, but also

that required concentrations of antibiotics may differ, in line with the operation undertaken, taking into account the duration of the procedure, the likely infecting organisms and the target tissue. Only local concentrations measured at the operation site and during the operation can confirm adequacy of applied doses and the need for additional doses to increase antibiotic concentrations. This study should therefore be regarded as the start for new studies that are urgently required to optimize the use of antibiotics during operations.

Declaration of interest None declared.

References 1. Himebauch A, Sankar W, Flynn J, et al. Skeletal Muscle and Plasma Concentrations of Cefazolin during Complex Paediatric Spinal Surgery. Br J Anaesth 2016; 117: 87–94 2. Proceedings of the International Consensus Meeting on Periprosthetic Joint Infection. https://www.efort.org/wpcontent/uploads/2013/10/Philadelphia_Consensus.pdf (accessed 15 March 2016) 3. Marculescu CE, Osmon DR. Antibiotic prophylaxis in orthopedic prosthetic surgery; Infect. Dis North Am 2005; 19: 931–46 4. Oishi CS, Carrion WV, Hoaglund FT. Use of parental prophylactic antibiotics in clean orthopaedic surgery. A review of the literature. Clin Orthop Rel Res 1993; 296: 249–55 5. Schurman DJ, Hirshman HP, Kajiyama G, Moser K, Burton DS. Cefazolin concentrations in bone and synovial fluid. J Bone Joint Surg Am 1978; 60: 359–62 6. Edmiston CE, Krepel C, Kelly H, et al. Perioperative antibiotic prophylaxis in the gastric bypass patient: do we achieve therapeutic levels? Surgery 2004; 136: 738–47 7. Claforan (Cefotaxime Sodium) for Injection Package Insert. Bridgewater, NJ: Sanofi Aventis, 2009 Jul http://www.accessdata.fda. gov/drugsatfda_docs/label/2008/050596s035,050547s066lbl. pdf (accessed 15th March 2016) 8. Pappas PG, Silveira FP. Candida in solid organ transplant recipients. Am J Transplant 2009; 9(suppl4): S173–9 9. Zelenitsky SA, Silverman RE, Duckworth H, et al. A prospective, randomized, double-blind study of single high dose versus multiple standard dose gentamicin both in combination with metronidazole for colorectal surgical prophylaxis. J Hosp Infect 2000; 46: 135–40 10. Zelenitsky SA, Ariano RE, Harding GK, et al. Antibiotic pharmacodynamics in surgical prophylaxis: an association between intraoperative antibiotic concentrations and efficacy. Antimicrob Agents Chemother 2002; 46: 3026–30 11. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Vancomycin therapeutic guidelines: a summary of consensus recommendations from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis 2009; 49: 325–7 12. Heydeman JS, Nelson BB. Short term preventive antibiotics. Clin Orthop Relat Res 1986; 205: 184–7 13. van Kasteren ME, Mannien J, Ott A, Kullberg BJ, de Boer AS, Gyssens JC. Antibiotic prophylaxis and the risk of surgical site infections following total hip arthroplasty: timely administration is the most important factor. Clin Infect Dis 2007; 44: 921–7

Editorials

14. Johnson DP. Antibiotic prophylaxis with cefuroxime in arthroplasty of the knee. J Bone Joint Surg Br. 1987; 69: 787–9 15. Prokuski L. Prophylactic antibiotics in orthopedic surgery. J Am Acad Orthop Surg 2008; 16: 283–93 16. Bratzel DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical

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Infection prevention Project. Clin Infect Dis 2004; 38: 283–93 17. Zanetti G, Giardina R, Platt R. Intraoperative redosing of cefalozin and risk for surgical site infection in cardiac surgery. Emerg Infect Dis 2001; 7: 828–31

British Journal of Anaesthesia 117 (1): 5–7 (2016) Advance Access publication 20 May 2016 . doi:10.1093/bja/aew107

Need to consider human factors when determining first-line technique for emergency front-of-neck access A. Timmermann1,*, N. Chrimes2 and C. A. Hagberg3 1

Department of Anaesthesia, Pain Therapy, Intensive Care and Emergency Medicine, Red Cross Clinic Berlin Westend und Mitte, Berlin, Germany, 2 Department of Anaesthesia, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, VIC 3168, Australia, and 3 Department of Anesthesiology, UT Health, McGovern Medical School, 6431 Fannin Street, MSB 5.020, Houston, TX 77030, USA *Corresponding author. E-mail: [email protected]

Emergency cricothyroidotomy is a temporary, life-saving procedure, indicated immediately when the airway is obstructed and oxygen delivery is unable to be restored by other means. It is therefore the final step in the guidelines for the management of difficult airways, reserved for can’t intubate, can’t oxygenate (CICO) emergencies. Debate over whether use of a cannula or scalpel provides the best technique for emergency front-of-neck access by anaesthetists in these circumstances must logically consider the likelihood of technical success of each of these methods. The effectiveness of either technique as a rescue strategy is also dependent, however, on a clinician’s willingness to implement it. The recently published 2015 Guidelines of the Difficult Airway Society (DAS) endorse scalpel cricothyroidotomy as the sole method for emergency front-of-neck access.1 This editorial addresses the possible implications of this decision on the psychological preparedness of clinicians to undertake the transition to emergency surgical airway. The updated DAS Guidelines acknowledge that much of the data for this recommendation comes from sources which cannot be translated directly to inhospital anaesthetic practice.1 The lack of clear technical superiority of one technique over the other, combined with the knowledge that the decision to perform front-of-neck access is frequently undertaken too late or not at all,2–4 further increases the weight that must be given to the impact that these techniques might have on a clinician’s ‘willingness to act’ in the CICO scenario. Appropriate decision-making, availability of equipment, technical ability, and human factors considerations, all supported by regular training, are essential for successful performance of front-of-neck access techniques when a CICO event occurs. As such, the following considerations potentially make a cannula-based technique more suitable than the scalpel-based technique for the anaesthetist in their initial attempt at front-of-neck access.

Familiarity: as noted in the DAS guidelines,1 cannula-based techniques are already familiar to anaesthetists, which may lead to them being implemented sooner.5 (ii) Training: obtaining tracheal access with a cannula is a relatively low-risk procedure,6 which affords opportunities for regular practice on live human subjects in an elective setting (e.g. when performing a transtracheal block for awake intubation). Other than using a smaller-gauge cannula, the procedure may be performed in an identical manner to that used for emergency airway access and is fairly well tolerated by patients.7 The ability to practise this technique on patients would be expected to improve clinicians’ technical abilities. Importantly, it would also help to diminish the significant psychological barriers to undertaking front-of-neck access by reinforcing the minimally invasive nature of the procedure and improving familiarity and confidence. These opportunities are not available with the more traumatic scalpel techniques, in which complications are predominantly related to insertion rather than oxygen delivery.8 As such, scalpel techniques can be practised only using synthetic models, cadavers, or live animals. Given the limited access of most clinicians to live animal specimens, this largely restricts practice of scalpel technique to the bloodless field of synthetic or cadaveric airways, resulting in a significant loss of fidelity. This is likely to be pertinent to the ability to transfer these skills to clinical practice in an emergency airway situation. (iii) Pre-emptive use: the low-risk nature of cannula access6 8 provides the additional benefit that placement of a cricothyroid cannula is able to be instituted as a precaution, before a CICO situation develops. Such pre-emptive use may be undertaken in periods of confirmed alveolar oxygen delivery during the process of managing the difficult airway and has even been advocated as an option before induction of anaesthesia in patients with a suspected difficult airway.2

(i)