The diagnosis, treatment and impact of hyperosmolar hyperglycaemic syndrome (HHS)

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This proposal outlines the rationale for a dissertation comprising a systematic review of contemporary literature that answers a research question relating to the diagnosis, treatment and impact of hyperosmolar hyperglycaemic syndrome (HHS), a rare complication of diabetes mellitus (DM). In the UK, more than 3.5 million people were diagnosed with DM in 2015 (Diabetes UK, 2016). Of these, a proportion risk developing HHS. The latter is an uncommon diabetic emergency that differs from diabetic ketoacidosis (DKA), a second cause of diabetic emergency (Scott, 2015). Although relatively rare, the 58% mortality associated with HHS is significantly higher than the 3-5% associated with DKA (Scott, 2015; Misra & Oliver, 2015). The basis of the pathological development of HHS instead of DKA is not fully understood, although HHS is more common in the elderly, and certain risk factors appear to act as triggers, such as trauma, surgery and infection (Kitabchi et al., 2009). There is considerable scope for the provision of evidence based knowledge to inform quality nursing care of HHS patients, and prevent inappropriate treatment of HHS using DKA based protocols, which could be fatal.


Normally, glucose released from carbohydrate digestion in the intestine enters the blood, stimulating insulin production by the pancreas (Barrett 2010). Insulin causes cells in the liver, skeletal, cardiac and smooth muscle to take up glucose, reducing its plasma concentration to within optimal homeostatic range (Wass & Owen 2014). Failure of this homeostatic negative feedback loop to maintain blood glucose within limits of 3-8 mmol/L can allow glucose to accumulate in blood plasma (hyperglycaemia), leading to polyuria, ketosis, acidosis (termed ‘diabetic ketoacidosis’ (DKA)) and coma, if not treated (Nazarko, 2009).

HHS may represent the first signs of previously undiagnosed DM, and has a slower onset than DKA; typically HHS develops over several days, whereas the onset of DKA is usually over hours (Scott, 2015; Kitabchi, et al, 2009). The latter authors suggest that the prolonged accumulation of the metabolic anomalies and dehydration that arise in HHS are a key feature of the condition, which according to Scott (2015), has yet to receive a consensual definition. These issues pose challenges to HHS diagnosis and treatment, compared to DKA. Typically, very high levels of blood glucose, (with a mean value 55 mmol/L (Gill and Alberti, 1985)), arise in HHS, above the levels normally observed in DKA. A key defining pathophysiological feature of the two conditions is the presence of plasma ketones; in HHS, these are not observed or are negligible (Scott & Claydon, 2012). This is not the case in DKA, in which ketones in plasma are significant, can often be smelt on the breath of DKA patients and can be measured in substantial amounts in urine (Scott & Claydon, 2012).

The Joint British Diabetes Societies Inpatient Care Group (Scott, & Claydon, 2012) recommend that, unlike those for DKA, treatment for HHS comprises fluid replacement, without insulin. Therefore, the treatment guidelines for HHS differ significantly from the treatment of DKA recommended by the National Institute of Care Excellence (NICE, 2015). Currently, there are no treatment guidelines for HHS provided by NICE, and, although The Joint British Diabetes Societies Inpatient Care Group (Scott, & Claydon, 2012) make recommendations to prevent oedema as part of fluid resuscitation in HHS treatment, opinions differ between American and European authors (Kitabchi et al., 2009; Milionis et al., 2001).

In view of the crucial differences in the treatment necessary to reduce the high mortality rate associated with HHS, distinguishing it from DKA as early as possible is crucial. It is imperative that nurses working in acute care areas such as emergency departments (EDs), are aware of both potential causes of diabetic medical emergency, and are able to distinguish between them in order to identify and prevent the inappropriate treatment of HHS.

Currently the knowledge base that enables nurses to achieve this appearsto be lacking in consensus and somewhat incongruent; for example, differing views of fluid resuscitation to treat HHs are proposed by American authors compared to those based in Europe (Kitabchi, et al., 2009; Milionis et al., 2001). Scrutiny of the Cochrane Database of Systematic Reviews (Cochrane Library, 2017) by this author revealed that there are currently no published systematic reviews indexed that provide any consensus on HHS diagnosis and treatment, as distinguished from that of DKA. This represents a significant knowledge gap that this dissertation aims to address.

The dissertation will comprise a systematic review, defined by Bettany-Saltikov (2012:5) as “A summary of the research literature that is focused on a single question”.

The dissertation will thus evaluate secondary quantitative research evidence that addresses one research question relating to the care of patients with HHS patients within the ED, from a nursing perspective. The following proposal outlines the content of the dissertation divided into chapters entitled ‘Background and Introduction’, ‘Methods’, ‘Results’, ‘Discussion’ and ‘Conclusions’, recommended by Walliman, (2004) and Greetham (2014).

The Dissertation ‘Abstract and Introduction’ (Chapter (Ch)1).

An abstract will precede the general introduction to the dissertation, and will provide a theoretical background, in which the the pathophysiology and risk factors associated with the development of HHS will be summarised, and compared and with those of DKA. The important distinction between these two diabetic emergencies in terms of diagnosis and treatment will be emphasised, reflecting the importance of their specific management to achieve positive patient outcomes. The abstract will outline the psychosocial impact of HHS on patients, and identify the significance of HHS as an emerging public health problem, both globally and in the UK., as rates of DM increase across all age groups (Rosenbloom, 2010). Initiatives described by the literature designed to reduce the incidence of DM and HHS are introduced prior to further discussion and evaluation in the dissertation.

Ethical approval will be considered in the introduction that will follow the abstract, emphasising that, although this is not necessary for the dissertation, which will be based upon secondary research, ethical approval for primary studies selected for review will be included within their critique, comprising the results chapter (Ch. 3).

The introduction will draw upon the information presented in the abstract to provide a rationale for the study and state the objective of the dissertation. This is to review contemporary research literature informing the diagnosis and treatment of HHS and DKA, identifying key differences. In summarising this information, the dissertation aims to contribute to evidence based knowledge that has the potential to improve nursing care of HHS patients, and positively influence treatment outcomes.  This will be achieved by formulating a specific relevant research question, that will be presented in the methods section (Ch 2). In the absence of requirements for a timeline for completion of the dissertation, the introduction will conclude by outlining the structure of the remaining dissertation. This will comprise a brief summary of the content of the remaining chapters, (as outlined below).

Should a timescale for completion of the thesis is required, this will conclude the introduction and assume a commonly accepted format, such as a Gantt chart (cited by Wilson, 2003).

Dissertation ‘Methods’ section (Ch. 2)

The dissertation methods chapter will outline the formulation of the research question (below) using Bailey’s (1997) process to provide initial focus, followed by further refinement using the Population, Intervention (or ‘issue’), Comparative intervention and Outcome (‘PICO’) system (Khan et al., 2003). The use of PICO to guide the literature search strategy will be described in this chapter. The search of three databases, including the Cumulative Index of Nursing and Allied Health literature (‘CINAHL’) (Ebsco Health, 2016), Medline (Ebsco Health, 2017) and the Excerpta Medica dataBASE (‘Embase’), (Elsevier, 2017), to retrieve all relevant literature will be justified. The importance of avoiding the introduction of researcher bias through the application of inadequate or ineffective search strategies, and the need for transparency in search strategy reporting will be emphasised. In reflection of this discussion, all inclusion and exclusion criteria that will be applied throughout the search will be listed and justified.

Using Bailey’s (1997) process, and PICO (Khan et al., 2003), the specific research question will be:

In adults and children with diagnosed (or undiagnosed) DM (‘P’), what aspects of the diagnosis, treatment and management (‘I’) of HHS should differ from that of DKA (‘C’) in order to reduce mortality due to HHS (‘O’)?

The methods section will conclude by summarising how relevant studies selected for review were isolated using a ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses (‘PRISMA’) diagram, advocated by Moher, et al., (2009) and widely applied by systematic reviews published by the Cochrane database (Higgins and Green, 2011). The method of data extraction suggested by Higgins and Green, (2011) will be applied, and the results discussed in the chapter 3.

Dissertation ‘Results’ section (Ch. 3)

The results section will initially present the findings of data extraction in which the type of each research study (for example, cohort study or randomised control trial (RCT), geographical location, population size and findings are summarised.

Critical appraisal of research is important to establish its validity, generalizability and its capacity to safely and reliably inform healthcare practice (Corrall, 2002; Taylor et al., 2004). In order to assess the quality of research and prevent reviewer bias, validated critiquing tools will be applied. These will comprise study-design specific Critical Appraisal Skill Programme (‘CASP) checklists which, according to Ciliska et al., (2010) have been widely applied to evaluate primary healthcare research, and are validated for use in this context.

Dissertation Discussion (Ch.4)

This chapter will begin with an introductory summary in which the research question is revisited and a summary of the findings of the literature review provided. These findings will be related to how well they addressed the research question, identifying any gaps in the literature that prevented it being fully answered, if relevant. Bettany-Saltikov (2012) suggests discussing the types of research design used by the studies reviewed, and then discussing how the findings from each study informed an answer. This introductory summary section will, therefore, relate the findings of quantitative study types such as RCTs and cohort studies to the research question and consider their relative contributions towards providing an answer.

The discussion chapter will proceed, as recommended by Bettany-Saltikov (2012), to discuss the results in the previous chapter in the same order in which they were presented. Therefore, the search results will be discussed briefly, including a rationale for why specific papers were selected for review. The rationale for article inclusion or exclusion will be considered in greater detail to retain transparency and prevent reviewer bias, extending the outline provided in chapter 2. The critical appraisal of specific studies selected will then be discussed more fully, identifying each study’s strengths and weaknesses, conflicting data and/or findings and highlighting any pertinent ethical issues. Finally, the discussion of the results will provide a synthesis of the overall findings in relation to elements of PICO (Khan et al., 2003).

Any methodological limitations associated with the search strategy, such as potential reviewer bias, will be discussed in this chapter. This is important because bias can influence the interpretation of the results, causing readers to be misled (Parahoo, 2014). The means to obviate any identified reviewer bias or other limitations in future research will be considered, in addition to making recommendations related to any of the reviewed studies in which bias could have influenced the research findings.

The discussion chapter will include an ‘implications for practice’ section that will consider how the findings synthesised from the review relate to nursing practice. This part of the discussion is crucial, in that the purpose of the review is to improve practice and patient outcomes and prevent poor outcomes associated with the application of practice that has no evidence base.

The findings of the review will be related more widely to local care standards prescribed by clinical governance and the role of nursing as outlined in healthcare policy, such as the Five Year Forward View (NHS England, 2014). In addition, the findings will be discussed in relation to the standards for the treatment of diabetic emergencies recommended by the National Institute of Clinical Excellence (NICE, 2015), and the Joint British Diabetes Societies Inpatient Care Group (Scott, & Claydon, 2012).

The discussion chapter will conclude with recommendations for future research based upon what is, and is not, known about the diagnosis, treatment and impact of HHS (compared to DKA) evident from the literature review. The focus of these recommendations will be on identifying research necessary to improve the practice of nurses working in EDs who encounter patients experiencing HHS and support their ability to deliver high quality, evidence based care as demanded by the NMC (2015).

Dissertation Conclusion (Ch. 5)

No new information will be presented in this chapter; rather, this final part of the dissertation will review the original objective outlined in the introduction, restate the main findings of the literature review, and consider how well these answer the research question. The most significant recommendations that could be made to improve practice will be emphasised, highlighting, research likely to be most beneficial to future practice.

Key ethical issues that must be considered when researching care related to HHS and DKA suffers discussed in chapter 3 will be reiterated, and the most significant strengths and weaknesses of the literature review (identified in chapter 4) will be reiterated.


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Barrett, K.E., 2010. Ganong's review of medical physiology. McGraw-Hill Education, Maidenhead (UK)

Bettany-Saltikov, J., 2012. How to do a systematic literature review in nursing: a step-by-step guide. McGraw-Hill Education. Maidenhead, (UK).

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Corrall, C.J., Wyer, P.C., Zick, L.S. and Bockrath, C.R., 2002. How to find evidence when you need it, part 1: databases, search programs, and strategies. Annals of emergency medicine, 39(3), pp.302-306

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Kitabchi, A.E., Umpierrez, G.E., Miles, J.M. and Fisher, J.N., 2009. Hyperglycemic crises in adult patients with diabetes. Diabetes care, 32(7), pp.1335-1343.

Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G. and Prisma Group, 2009. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS medicine, 6(7), p.e1000097.

Milionis, H.J., Liamis, G. and Elisaf, M.S., 2001. Appropriate treatment of hypernatraemia in diabetic hyperglycaemic hyperosmolar syndrome. Journal of internal medicine, 249(3), pp.273-274.

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Parahoo, K., 2014. Nursing research: principles, process and issues. Palgrave Macmillan. London.

Rosenbloom, A.L., 2010. Hyperglycemic hyperosmolar state: an emerging pediatric problem. The Journal of pediatrics, 156(2), pp.180-184.

Scott, A.R., 2015. Management of hyperosmolar hyperglycaemic state in adults with diabetes. Diabetic Medicine, 32(6), pp.714-724.

Scott, A., Claydon, A. (2012) The management of hyperosmolar hyperglycaemic state (HHS) in adults with diabetes. Joint British Diabetes Societies Inpatient Care Group [online] Available at: Accessed 26 June 2017.

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