Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-13T00:55:13.992Z Has data issue: false hasContentIssue false

Chapter 14 - Therapeutic Options in Neurocritical Care

Beyond the Brain

Published online by Cambridge University Press:  28 April 2020

By
Aggie Skorko ,
Matthew J. C. Thomas ,
Elfyn Thomas  and
Richard Protheroe
Edited by
Peter C. Whitfield ,
Jessie Welbourne ,
Elfyn Thomas ,
Fiona Summers ,
Maggie Whyte  and
Peter J. Hutchinson
Peter C. Whitfield
Affiliation:
Derriford Hospital, Plymouth
Jessie Welbourne
Affiliation:
University Hospitals, Plymouth
Elfyn Thomas
Affiliation:
Derriford Hospital, Plymouth
Fiona Summers
Affiliation:
Aberdeen Royal Infirmary
Maggie Whyte
Affiliation:
Aberdeen Royal Infirmary
Peter J. Hutchinson
Affiliation:
Addenbrooke’s Hospital, Cambridge
Get access

Summary

It has long been recognised that a neurological injury can elicit profound systemic complications, from Harvey Cushing who in 1903 described strategies to limit fatal haemodynamic dysfunction during surgical CNS surgery to reports of pulmonary oedema post-seizures in 1908.1

Studies of patients admitted to intensive care with traumatic brain injury (TBI) showed that up to 89% developed non-neurological organ dysfunction, worsening their outcome.2,3 Most commonly patients develop sepsis, respiratory or cardiovascular complications with rates of 75%, 41% and 44% respectively in one cohort.3 Renal and hepatic system involvement is much less common.4 The presence of hypotension, severe respiratory failure or sepsis has been shown to be independent predictors of death and mortality rates rise from 31%–40% for single organ failure to 47%–91% with two organ system failures and up to 100% in cases with three or more organ system failures.

Type
Chapter
Information
Traumatic Brain Injury
A Multidisciplinary Approach
 , pp. 164 - 185
Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Davison, DL, Terek, M, Chawla, LS. Neurogenic pulmonary edema. Crit Care 2012;16(2):212.Google Scholar
Zygun, D. Non-neurological organ dysfunction in neurocritical care: impact on outcome and etiological considerations. Curr Opin Crit Care 2005;11(2):139–43.CrossRefGoogle ScholarPubMed
Corral, L, Javierre, CF, Ventura, JL, Marcos, P, Herrero, JI, Mañez, R. Impact of non-neurological complications in severe traumatic brain injury outcome. Crit Care 2012;16(2):R44.CrossRefGoogle ScholarPubMed
Lim, HB, Smith, M. Systemic complications after head injury: a clinical review. Anaesthesia 2007;62(5):474–82.CrossRefGoogle ScholarPubMed
Zygun, DA, Kortbeek, JB, Fick, GH, Laupland, KB, Doig, CJ. Non-neurologic organ dysfunction in severe traumatic brain injury. Crit Care Med 2005;33(3):654–60.CrossRefGoogle ScholarPubMed
Brouwers, PJ, Wijdicks, EF, Hasan, D, Vermeulen, M, Wever, EF, Frericks, H, et al. Serial electrocardiographic recording in aneurysmal subarachnoid hemorrhage. Stroke 1989;20(9):1162–7.CrossRefGoogle ScholarPubMed
Macmillan, C, Grant, I, Andrews, P. Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active management? Intens Care Med 2002;28(8):1012–23.CrossRefGoogle ScholarPubMed
Bruder, N, Rabinstein, A. Cardiovascular and pulmonary complications of aneurysmal subarachnoid hemorrhage. Neurocrit Care 2011;15(2):257.CrossRefGoogle ScholarPubMed
Dujardin, KS, McCully, RB, Wijdicks, EFM, Tazelaar, HD, Seward, JB, McGregor, CGA, et al. Myocardial dysfunction associated with brain death: clinical, echocardiographic, and pathologic features. J Heart Lung Transpl 2001;20(3):350–7.CrossRefGoogle ScholarPubMed
Prathep, S, Sharma, D, Hallman, M, Joffe, A, Krishnamoorthy, V, Mackensen, GB, et al. Preliminary report on cardiac dysfunction after isolated traumatic brain injury. Crit Care Med 2014;42(1):10.1097/CCM.0b013e318298a890.CrossRefGoogle ScholarPubMed
Hasanin, A, Kamal, A, Amin, S, Zakaria, D, El Sayed, R, Mahmoud, K, et al. Incidence and outcome of cardiac injury in patients with severe head trauma. Scand J Trauma Resuscitation Emerg Med 2016;24:58.Google Scholar
Biso, S, Wongrakpanich, S, Agrawal, A, Yadlapati, S, Kishlyansky, M, Figueredo, V. A review of neurogenic stunned myocardium. Cardiovasc Psychiatr Neurol 2017;2017:5842182.Google ScholarPubMed
Hu, PJ, Pittet, JF, Kerby, JD, Bosarge, PL, Wagener, BM. Acute brain trauma, lung injury, and pneumonia: more than just altered mental status and decreased airway protection. Am J Physiol Lung Cell Molecul Physiol 2017;313(1):L1–l15.CrossRefGoogle ScholarPubMed
Carney, N, Totten, AM, O’Reilly, C, Ullman, JS, Hawryluk, GW, Bell, MJ, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2017;80(1):6–15.CrossRefGoogle ScholarPubMed
Contant, CF, Valadka, AB, Gopinath, SP, Hannay, HJ, Robertson, CS. Adult respiratory distress syndrome: a complication of induced hypertension after severe head injury. J Neurosurg 2001;95(4):560–8.CrossRefGoogle ScholarPubMed
Stover, JF, Steiger, P, Stocker, R. Controversial issues concerning norepinephrine and intensive care following severe traumatic brain injury. Eur J Trauma 2006;32(1):10–27.Google Scholar
Steiner, LA, Johnston, AJ, Czosnyka, M, Chatfield, DA, Salvador, R, Coles, JP, et al. Direct comparison of cerebrovascular effects of norepinephrine and dopamine in head-injured patients. Crit Care Med 2004;32(4):1049–54.CrossRefGoogle ScholarPubMed
Deehan, SC, Grant, IS. Haemodynamic changes in neurogenic pulmonary oedema: effect of dobutamine. Intens Care Med 1996;22(7):672–6.CrossRefGoogle ScholarPubMed
Sakr, Y, Reinhart, K, Vincent, J-L, Sprung, CL, Moreno, R, Ranieri, VM, et al. Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) study. Crit Care Med 2006;34(3):589–97.Google Scholar
Gordon, AC, Mason, AJ, Thirunavukkarasu, N, et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the vanish randomized clinical trial. JAMA 2016;316(5):509–18.CrossRefGoogle ScholarPubMed
Mrozek, S, Srairi, M, Marhar, F, Delmas, C, Gaussiat, F, Abaziou, T, et al. Successful treatment of inverted Takotsubo cardiomyopathy after severe traumatic brain injury with milrinone after dobutamine failure. Heart Lung 2016;45(5):406–8.Google Scholar
Farmakis, D, Alvarez, J, Gal, TB, Brito, D, Fedele, F, Fonseca, C, et al. Levosimendan beyond inotropy and acute heart failure: evidence of pleiotropic effects on the heart and other organs: An expert panel position paper. Int J Cardiol 2016;222:303–12.CrossRefGoogle Scholar
Romero, CM, Morales, D, Reccius, A, Mena, F, Prieto, J, Bustos, P, et al. Milrinone as a rescue therapy for symptomatic refractory cerebral vasospasm in aneurysmal subarachnoid hemorrhage. Neurocrit Care 2009;11(2):165–71.CrossRefGoogle ScholarPubMed
Alali, AS, McCredie, VA, Golan, E, Shah, PS, Nathens, AB. Beta blockers for acute traumatic brain injury: a systematic review and meta-analysis. Neurocrit Care 2014;20(3):514–23.Google Scholar
Esnault, P, Nguyen, C, Bordes, J, D’Aranda, E, Montcriol, A, Contargyris, C, et al. Early-onset ventilator-associated pneumonia in patients with severe traumatic brain injury: incidence, risk factors, and consequences in cerebral oxygenation and outcome. Neurocrit Care 2017;27(2):187–98.Google Scholar
Bronchard, MDR, Albaladejo, MDPDP, Brezac, MDG, Geffroy, MDA, Seince, MDP-F, Morris, MDW, et al. Early onset pneumoniarisk factors and consequences in head trauma patients. Anesthesiology 2004;100(2):234–9.Google Scholar
Daneman, N, Sarwar, S, Fowler, RA, Cuthbertson, BH. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infectious Dis 2013;13(4):328–41.Google ScholarPubMed
Chan, EY, Ruest, A, Meade, MO, Cook, DJ. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. Br Med J 2007;334(7599):889.CrossRefGoogle ScholarPubMed
Force ADT. Acute respiratory distress syndrome. JAMA 2012;307(23):2526–33.Google Scholar
Roth, C, Ferbert, A, Deinsberger, W, Kleffmann, J, Kästner, S, Godau, J, et al. Does prone positioning increase intracranial pressure? A retrospective analysis of patients with acute brain injury and acute respiratory failure. Neurocrit Care 2014;21(2):186–91.CrossRefGoogle ScholarPubMed
Tejerina, E, Pelosi, P, Muriel, A, Peñuelas, O, Sutherasan, Y, Frutos-Vivar, F, et al. Association between ventilatory settings and development of acute respiratory distress syndrome in mechanically ventilated patients due to brain injury. J Crit Care 2017;38:341–5.Google Scholar
Young, NH, Andrews, PJD. High-frequency oscillation as a rescue strategy for brain-injured adult patients with acute lung injury and acute respiratory distress syndrome. Neurocrit Care 2011;15(3):623–33.CrossRefGoogle ScholarPubMed
Hssain, AA, Raza, TM. ECMO in trauma patients: future may not be bleak after all!Qatar Med J 2017;2017(1):6.CrossRefGoogle Scholar
Munoz-Bendix, C, Beseoglu, K, Kram, R. Extracorporeal decarboxylation in patients with severe traumatic brain injury and ARDS enables effective control of intracranial pressure. Crit Care 2015;19(1):381.Google Scholar
Geerts, WH, Bergqvist, D, Pineo, GF, Heit, JA, Samama, CM, Lassen, MR, et al. Prevention of venous thromboembolism. Chest 2008;133(6):381S–453S.Google Scholar
Barrera, LM, Perel, P, Ker, K, Cirocchi, R, Farinella, E, Morales Uribe, CH. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev 2013(3).Google Scholar
Prophylaxis of venous thrombosis in neurocritical care patients: an evidence-based guidelines: a statement for healthcare professionals from the neurocritical care society. P Nyquist et at. Neurocrit Care 2016;24:47–60.Google Scholar
Young, D, Harrison, DA, Cuthbertson, BH, Rowan, K, TracMan Collaborators. Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial. JAMA 2013;309(20):2121–9.Google Scholar
Death NCEiPOa. On the right Trach? A review of the care of patients who underwent a tracheostomy. London; 2014.Google Scholar
Oliver, ER, Gist, A, Gillespie, MB. Percutaneous versus surgical tracheotomy: an updated meta-analysis. Laryngoscope 2007;117(9):1570–5.Google Scholar
Brass, P, Hellmich, M, Ladra, A, Ladra, J, Wrzosek, A. Percutaneous techniques versus surgical techniques for tracheostomy. Cochrane Database Syst Rev 2016(7).Google ScholarPubMed
Stocchetti, N, Parma, A, Lamperti, M, Songa, V, Tognini, L. Neurophysiological consequences of three tracheostomy techniques: a randomized study in neurosurgical patients. J Neurosurg Anesthesiol 2000;12(4):307–13.CrossRefGoogle ScholarPubMed
Reilly, PM, Sing, RF, Giberson, FA, Anderson III, HL, Rotondo, MF, Tinkoff, GH, et al. Hypercarbia during tracheostomy: a comparison of percutaneous endoscopic, percutaneous Doppler, and standard surgical tracheostomy. Intens Care Med 1997;23(8):859–64.CrossRefGoogle ScholarPubMed
Putensen, C, Theuerkauf, N, Guenther, U, Vargas, M, Pelosi, P. Percutaneous and surgical tracheostomy in critically ill adult patients: a meta-analysis. Crit Care 2014;18(6):544.CrossRefGoogle ScholarPubMed
Koitschev, A, Simon, C, Blumenstock, G, Mach, H, Graumuller, S. Suprastomal tracheal stenosis after dilational and surgical tracheostomy in critically ill patients. Anaesthesia 2006;61(9):832–7.CrossRefGoogle ScholarPubMed
Law, RC, Carney, AS, Manara, AR. Long-term outcome after percutaneous dilational tracheostomy. Anaesthesia 1997;52(1):51–6.Google Scholar
Young, E, Pugh, R, Hanlon, R, O’Callaghan, E, Wright, C, Jeanrenaud, P, et al. Tracheal stenosis following percutaneous dilatational tracheostomy using the single tapered dilator: an MRI study. Anaesth Intens Care 2014;42(6):745–51.CrossRefGoogle ScholarPubMed
Keren, C, Lazar-Zweker, G. Tracheotomy in severe TBI patients: sequelae and relation to vocational outcome. Brain Injury 2001;15(6):531–6.CrossRefGoogle ScholarPubMed
McCredie, VA, Alali, AS, Scales, DC, Adhikari, NKJ, Rubenfeld, GD, Cuthbertson, BH, et al. Effect of early versus late tracheostomy or prolonged intubation in critically ill patients with acute brain injury: a systematic review and meta-analysis. Neurocrit Care 2017;26(1):14–25.Google Scholar
Norton, JA, Ott, LG, McClain, C. The metabolic response to brain injury. JPEN 1987;11:488.Google Scholar
Clifton, GL, Robertson, CS, Grossman, RG. et al. The metabolic response to severe head injury. J Neurosurg 1984;60:687.Google Scholar
Deutschman, CS, Konstantinides, FN, Raup, S, Cerra, FB. Physiological and metabolic response to isolated closed-head injury: part 1: basal metabolic state: correlation of metabolic and physiologic parameters with fasting and stressed controls. J Neurosurg 1986;64:89.Google Scholar
Twyman, D. Nutritional management of the critically ill neurologic patient. Crit Care Clin 1997;13:39.Google Scholar
https://braintrauma.org/uploads/03/12/Guidelines_for_Management_of_Severe_TBI_4th_Edition.pdfGoogle Scholar
Yanagawa, T, Bunn, F, Roberts, I, Wentz, R, Pierro, A. Nutritional support for head-injured patients. Cochrane Database Syst Review 2003;CD001530.Google Scholar
Borzotta, AP, Pennings, J, Papasadero, B, Paxton, J, Mardesic, S, Borzotta, R, Parrott, A, Bledsoe, F. Enteral versus parenteral nutrition after severe closed head injury. J Trauma 1994;37:459–68.Google Scholar
Perel, P, Yanagawa, T, Bunn, F, Roberts, I, Wentz, R, Pierro, A. Nutritional support for head-injured patients. Cochrane Database Syst Rev 2006;4:CD001530.Google Scholar
Wang, X, Dong, Y, Han, X, Qi, XQ, Huang, CG, Hou, LJ. Nutritional support for patients sustaining traumatic brain injury: a systematic review and meta-analysis of prospective studies. PLoS One 2013;8(3):e58838.Google Scholar
Hadley, MN, Grahm, TW, Harrington, T, et al. Nutritional support and neurotrauma: a critical review of early nutrition in forty-five acute head injury patients. Neurosurgery 1986;19:367.Google Scholar
Duke, JH Jr, Jorgensen, SD, Broell, JR. Contribution of protein to caloric expenditure following injury. Surgery 1970;68:168.Google Scholar
Clifton, GL, Robertson, CS, Constant, DF. Enteral hyperalimentation in head injury. J Neuro-surg 1985;62:186.Google Scholar
Young, B, Ott, L, Twyman, D, et al. The effect of nutritional support on outcome from severe head injury. J Neurosurg 1987;67:668.Google Scholar
Glaesener, JJ, Fredebohm, M. Percutaneous endoscopic gastrostomy in the rehabilitation of neurological disorders. J Suisse Med 1992;122:1600.Google ScholarPubMed
Norton, JA, Ott, LG, McClain, C, et al. Intolerance to enteral feeding in the brain-injured patient. J Neurosurg 1998;68:62.Google Scholar
Ott, L, Young, B, Phillips, R, et al. Altered gastric emptying in the head injured patients: relationship to feeding intolerance. J Neurosurg 1991;74:738.Google Scholar
Marino, LV, Kiratu, EM, French, S, Nathoo, N. To determine the effect of metoclopramide on gastric emptying in severe head injuries: a prospective, randomized, controlled clinical trial. Br J Neurosurg 2003;17:24–8.Google Scholar
Kao, CH, Changlai, SP, Chieng, PU, Yen, TC. Gastric emptying in head-injured patients. Am J Gastroenterol 1998;93:1108–12.Google Scholar
Akkersdijk, WL, Roukema, JA, van der Werken, C. Percutaneous endoscopic gastrostomy for patients with several cerebral injury. Injury 1998;29:11.CrossRefGoogle ScholarPubMed
Kirby, DF, Clifton, GL, Turner, H, et al. Early enteral nutrition after brain injury by percutaneous endoscopic gastrojejunostomy. JPEN 1991;15:298.Google Scholar
Wahlstrom, MR, Olivecrona, M, Koskinen, LO, Rydenhag, B, Naredi, S. Severe traumatic brain injury in pediatric patients: treatment and outcome using an intracranial pressure targeted therapy - the Lund concept. Intensive Care Med 2005;31(6):832–9.Google Scholar
Grande, PO. Pathophysiology of brain insult: Therapeutic implications with the Lund Concept. Schweiz Med Wochenschr 2000;130(42):1538–43.Google Scholar
Clifton, GL, Miller, ER, Choi, SC, Levin, HS. Fluid thresholds and outcome from severe brain injury. Crit Care Med 2002;30(4):739–45.Google Scholar
Vedantam, A, Robertson, CS, Gopinath, SP. Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury. Neurosurg Focus 2017;43(5):E2.CrossRefGoogle ScholarPubMed
Adrogue, H, Madias, N. Hypernatremia. N Engl J Med 2000;342:1493–9.Google Scholar
Milionis, HJ, Liamis, G, Elisaf, MS. Hypernatremia in hospitalised patients: a sequel of inadvertent fluid administration. Arch Intern Med 2000;160:1541–2.CrossRefGoogle ScholarPubMed
Polderman, KH, Schreuder, WO, Strack van Schijndel, RJ, Thijs, LG. Hypernatremia in the intensive care unit: an indicator of quality of care? Crit Care Med 1999;27:1105–8.Google Scholar
Aiyagari, V, Deibert, E, Diringer, MN. Hypernatremia in the neurologic intensive care unit: how high is too high? J Crit Care 2006;21:163–72.Google Scholar
Crompton, MR. Hypothalamic lesions following closed head injury. Brain 1971;94:165–72.Google Scholar
Kern, K, Meislin, H. Diabetes insipidus: occurrence after minor head trauma. J Trauma 1984;24:69–72.CrossRefGoogle ScholarPubMed
Bondanelli, M, De Marinis, L, Ambrosio, MR, et al. Occurrence of pituitary dysfunction following traumatic brain injury. J Neurotrauma 2004; 21:685-96.Google Scholar
Capatina, C, Paluzzi, A, Mitchell, R, Karavitaki, N. Diabetes insipidus after traumatic brain injury. J Clin Med 2015;4(7):1448–62.Google Scholar
Stern, RH. Disorders of plasma sodium. N Engl J Med 2015;372:55–65.Google Scholar
Maggiore, U, Picetti, E, Antonucci, E, Parenti, E, Regolisti, G, Mergoni, M, Vezzani, A, Cabassi, A, Fiaccadori, E. The relation between the incidence of hypernatremia and mortality in patients with severe traumatic brain injury. Crit Care 2009;13:R110.Google Scholar
Grant, P, Ayuk, J, Bouloux, P-M, Cohen, M, Cranston, I, Murray, RD, Rees, A, Thatcher, N, Grossman, G. The diagnosis and management of inpatient hyponatraemia and SIADH. Eur J Clin Invest 2015;45(8):888–94.Google Scholar
Rajagopal, R, Swaminathan, G, Nair, S, Joseph, M. Hyponatremia in traumatic brain injury: a practical management protocol. World Neurosurg 2017;108:529–33.Google Scholar
Katz, MA. Hyperglycemia-induced hyponatraemia – calculation of expected serum sodium depression. N Engl J Med 1973;289:843–4.Google Scholar
Adrogue, HJ, Madias, NE. Hyponatremia. N Engl J Med 2000; 342:1581–1589.CrossRefGoogle ScholarPubMed
Peters, JP, Welt, LG, Sims, EA, Orloff, J, Needham, J. A salt-wasting syndrome associated with cerebral disease. Trans Assoc Am Physicians 1950;63:57–64.Google Scholar
Oh, MS, Carroll, HJ. Disorders of sodium metabolism: hypernatraemia and hyponatraemia. Crit Care Med 1992; 20:94–103.Google Scholar
Palmer, BF. Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab 2003;14(4):182.Google Scholar
Harrigan, MR. Cerebral salt wasting syndrome. Crit Care Clin 2001;17:125–38.CrossRefGoogle ScholarPubMed
Hannon, MJ, Thompson, CJ. Neurosurgical hyponatremia. J Clin Med 2014;3(4):1084–104.Google Scholar
Cole, CD, Gottfried, ON, Liu, JK, Couldwell, WT. Hyponatremia in the neurosurgical patient: diagnosis and management. Neurosurg Focus 2004;16(4):E9.Google Scholar
Schrier, RW, Gross, P, Gheorghiade, M, Berl, T, Verbalis, JG, Czerwiec, FS, Orlandi, C. Tolvaptan, a selective oral vasopressin v2-receptor antagonist, for hyponatremia. N Engl J Med 2006;355:2099–112.CrossRefGoogle ScholarPubMed
Human, T, Onuoha, A, Diringer, M, Dhar, R. Response to a bolus of conivaptan in patients with acute hyponatremia after brain injury. J Crit Care 2012:27(6):745.Google Scholar
Jeon, S-B, Choi, HA, Lesch, C, Kim, MC, Badjatia, N, Claassen, J, Mayer, SA, Lee, K. Use of oral vasopressin V2 receptor antagonist for hyponatremia in acute brain injury. Eur Neurol 2013;70:142–8.Google Scholar
Brunner, JE, Redmond, JM, Haggar, AM, Kruger, DF, Elias, SB. Central pontine myelinolysis and pontine lesions after rapid correction of hyponatraemia: a prospective magnetic resonance imaging study. Ann Neurol 1990;27:61–6.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×