Fasting hyperglycemia upon hospital admission is associated with higher pneumonia complication rates among the elderly.

BACKGROUND: Hyperglycemia is an independent predictor of adverse outcomes during hospitalization. In patients who have pneumonia, significant hyperglycemia is associated with poor outcomes. This study evaluates the interaction of the degree of hyperglycemia and complication rates stratified by age in non-critically ill patients admitted to the hospital for care of community-acquired pneumonia.
METHODS: Retrospective review of patient records coded for pneumonia. Analysis included 501 non-critically ill patients admitted to a tertiary care hospital in New York City. Data were stratified by diabetes status, age (less than 65 and 65 and over), and fasting blood glucose (FBG) within the first 24 hours of hospitalization. Among patients with no history of diabetes, FBG was stratified as "normal" [FBG </=100 mg/dl (5.6 mmol/l)], "mild-hyperglycemia" [101-125 mg/dl (5.7-6.9 mmol/l)], and "severe-hyperglycemia" [>/=126 mg/dl (7 mmol/l)]. The diabetic group included known diabetics regardless of FBG. The Pneumonia Severity Index (PSI) was calculated for all patients. Complications rates, hospital length of stay and mortality were compared among the groups.
RESULTS: In patients age 65 and older, complication rates were 16.7% in normoglycemics, 27.5% in the "mild-hyperglycemia" group, 28.6% in the "severe hyperglycemia" group, and 25.5% in those with known diabetes. The mild and severe-hyperglycemics had similar complication rates (p = 0.94). Compared to the normal group, mild and severe groups had higher rates of complications, p = 0.05 and p = 0.03, respectively. PSI tended to be higher in those over the age of 65. PSI was not significantly different when the normal, mild, severe, and known diabetes groups were compared. PSI did not predict complications for new hyperglycemia (normals' mean score 87, mild 84.7, severe 93.9, diabetics 100). Hospital mortality did not differ among groups. Length of stay was longer (p = 0.05) among mild-hyperglycemics (days = 8.4 s.e. 14.3) vs. normals (days = 6.2 s.e.6.5).
CONCLUSION: This study shows that FBS between 101-125 mg/dl (5.7-6.9 mmol/l) on hospital admission increases pneumonia complication rates among the elderly with no previous diagnosis of diabetes.

Background

Pneumonia is the leading infectious cause of death in the elderly [1]. Annually, about 5 million Americans, mostly older adults, are diagnosed with pneumonia [2]. The presence of multiple chronic conditions, declining cough reflex, and impaired ciliary function make older individuals more susceptible to pneumonia and at increased risk for its complications [1,2].

Hyperglycemia is an independent predictor of adverse outcomes during hospitalization in multiple clinical settings, including acute myocardial infarction, stroke, and surgery [3-5]. Hospitalized individuals without a prior history of diabetes who are found to be hyperglycemic have increased mortality compared to known diabetics and those with normal glucose [6]. Hyperglycemic patients (admission blood glucose ≥ 200 mg/dl [11 mmol/l]) with community-acquired pneumonia have increased mortality and complications of pneumonia when compared to normoglycemic individuals [7].

At the molecular level, hyperglycemia affects pro-inflammatory cytokine production [8] and the function of polymorphonuclear leukocytes [9] and T cells [10]. Alterations in polymorphonuclear cells have been extensively studied, with demonstration of defects in adhesion, chemotaxis, and phagocytosis when cells are exposed to hyperglycemia [11], supporting clinically observed adverse outcomes. Observational studies associating hyperglycemia with poor patient outcome provided the basis for randomized controlled interventional studies [12-18], which have shown that treating hyperglycemia with insulin protocols improves the morbidity and mortality rates among post-operative patients in the surgical intensive care unit (ICU) and during critical illness. As a result of these studies, control of hyperglycemia during critical illness has become a standard of care. Although optimal glucose targets and protocols continue to be examined for critically ill patients, there are no interventional trials evaluating goals for glucose control in the non-intensive care setting. Observational studies found that admission glucose above 200 mg/dl (11 mmol/l) was a predictor of in-hospital complications and longer length of stay (LOS) [7]. However, there are no published studies examining whether mild hyperglycemia with fasting values between 100 mg/dl to 126 mg/dl (5.6-7 mmol/l) leads to adverse outcomes in hospitalized patients outside the intensive care setting. In this study, we evaluated patients admitted to general medical floors for the treatment of community-acquired pneumonia to determine if mild hyperglycemia affects morbidity and mortality.

Research Design and Methods

This study was conducted at a large teaching hospital. The hospital serves a mixed urban/suburban population of nearly half a million in a borough of New York City. The medical records of patients admitted for the treatment of pneumonia during one year were examined. Patients were identified by discharge diagnosis codes for pneumonia. Eligibility criteria were: age 18 years or older, placement on a general medical floor on admission, pneumonia diagnosed by the finding of a new infiltrate on chest x-ray as documented by a radiology report with clinical symptoms suggestive of a pulmonary infection; and having an early morning fasting blood glucose (FBG) level drawn within 24 hours of admission. Patients were excluded if they were being treated for a hospital-acquired pneumonia, defined as either developing a new pneumonia 48 hours or more after admission or within 2 weeks after discharge from a hospital. Patients admitted to a critical care unit were also excluded.

Patients who met the inclusion criteria were then grouped according to their FBG level as follows: 1. "Known diabetic": patients known to have a previous history of diabetes regardless of the admission FBG, 2. "Severe hyperglycemia": a group defined by FBG of 126 mg/dl (7 mmol/l) or greater and no previous history of diabetes, 3. "Mild hyperglycemia": a group defined by FBG of 101 mg/dl to 125 mg/dl (5.7-6.9 mmol/l) and no previous history of diabetes, 4. "Normal": a group defined by FBG of less than or equal to 100 mg/dl (5.6 mmol/l).

Pneumonia complications were defined as a change from the initial admission status by development of one or more of the following during the hospitalization: "Mild" complications: 1) Increase in oxygen requirement after 24 hours of admission, 2) Increased antibiotic coverage (defined as requiring an additional antibiotic added to the initial treatment or a switch to more broad-spectrum antibiotic coverage due to worsening clinical symptoms), "Severe" complications: 1) Transfer to an intensive care unit at any time during the hospitalization, 2) Need for mechanical ventilation, 3) Development of sepsis (based upon clinical signs and symptoms of having the systemic inflammatory response syndrome), 4) Death that occurred in the course of the hospitalization was included as a severe complication. All patients were managed according to pneumonia treatment guidelines published by the American Thoracic Society [19]. The three hyperglycemic groups were compared to the normoglycemic group in terms of these main outcome variables: frequency of pneumonia complications, hospital LOS and in-hospital death rate.

Because outcomes of pneumonia are known to be worse in the geriatric population [20], patients were stratified by age (less than 65 years old and 65 years of age and above).

Baseline Pneumonia Severity

The pneumonia severity index (PSI) [21-23] was used to stratify risk. This stratifies patients with pneumonia into five classes for the risk of death within 30 days of presentation. Predictor variables are based on the presence of co-morbidities, physical findings and selected laboratory tests, with points assigned for poor outcome variables. Blood glucose in this scoring system is considered poor if a random value is greater than 250 mg/dl (14 mmol/l).

Statistical analysis

The effects of mild and severe hyperglycemia on pneumonia outcome were determined by examining: the frequency of pneumonia complications, LOS and in-hospital death rate. The data were collected and statistical analysis was done to determine whether patients with any level of hyperglycemia admitted for pneumonia had a longer hospital stay, higher rate of complications, or an increased mortality compared to the control patients. The data was examined using The Epic Info Statistical Package 2000. Odds ratios (OR) were calculated for each group. Continuous data are presented as mean ± SD and compared via ANOVA with 3 groups. Pearson Chi Square test was used to compare the frequency of complications within the groups. The significance level was set at p < 0.05 for all analyses.

Results

A total of 2000 patient records were reviewed. Five hundred and one cases were included; the major reason for exclusion was the lack of a documented infiltrate on the chest x-ray report. Patients' characteristics are shown in Table 1.

Table 1

Characteristics of pneumonia patients admitted to general medical floors

		Admission glucose level (%)
		Normal≤100 mg/dlN = 56		Mild101-125 mg/dlN = 51		Severe>126 mg/dlN = 44		Known diabeticN = 37
Group		n	%	n	%	n	%	n	%
	Average Age (se)	50.5 (10.8)	-	46.7(13.5)	-	51 (10)	10.0	46.2 (10.4)	-
18-64	Gender
	Male	30	53.6	30	58.8	21	47.7	24	64.9
	Female	26	46.4	21	41.2	23	52.3	13	35.1
	History of COPD*	4	7.3	6	11.8	¶¶¶18	40.9	7	18.9
	Heart Failure	8	14.3	¶1	2.0	2	4.6	2	5.4
	Liver disease	6	10.7	2	3.9	3	6.8	4	10.8
	Cancer	5	8.9	3	5.9	4	9.1	2	5.4
	Chronic renal disease	10	17.9	4	7.8	3	6.8	9	24.3
	Mean PSI†	61.4 (se 4.1)		61.6 (se 4.1)		61.3 (se 4.4)		74.4 (se 4.2)
		N = 69		N = 68		N = 99		N = 77
		n	%	n	%	n	%	n	%
	Average Age (se)	78.2 (7.3)		80.9 (9.1)		80.6(8.6)		80.0 (7.4)
65 and Above	Gender
	Male	36	52.2	¶24	35.8	48	48.5	43	55.8
	Female	33	47.8	43	64.2	51	51.5	34	44.2
	Living arrangement
	Community	54	78.3	53	77.9	73	73.7	58	75.3
	Nursing home	15	21.7	5	22.1	26	26.3	19	24.7
	History of COPD†	19	27.5	19	28.0	30	30.6	14	18.2
	Heart Failure	18	26.1	10	14.7	¶13	13.1	22	28.6
	Liver disease	1	1.5	3	4.4	4	4.0	2	2.6
	Cancer	6	8.7	7	10.5	12	12.1	10	13.0
	Chronic renal disease	24	34.8	17	25.0	22	22.2	19	24.7
	PSI (mean se) *	107.8 (se = 4.5)		102.1 (se = 3.5)		108.4 (se = 3.4)		112.4 (se = 3.1)

†COPD, chronic obstructive pulmonary disease

*Pneumonia Severity Index (mean and standard error), t-test compares each group with the normal group (admission glucose ≤99 mg/dl), *p ≤ 0.05

¶χ2 tests compares each group with the normal group (admission glucose ≤99 mg/dl) ¶0.01

Note: Highlighted values were statistically different from the normal group; all others were not statistically significant

¶χ2 tests compares each group with the normal group (admission glucose ≤99 mg/dl) ¶0.01