Is there a difference between women and men in characteristics and outcome after in hospital cardiac arrest?

Is there a difference between women and men in characteristics and outcome after in hospital cardiac arrest?

Resuscitation 49 (2001) 15 – 23 www.elsevier.com/locate/resuscitation Is there a difference between women and men in characteristics and outcome afte...

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Resuscitation 49 (2001) 15 – 23 www.elsevier.com/locate/resuscitation

Is there a difference between women and men in characteristics and outcome after in hospital cardiac arrest? J. Herlitz *, S. Rundqvist, A. Ba˚ng, S. Aune, G. Lundstro¨m, L. Ekstro¨m, J. Lindkvist Di6ision of Cardiology, Sahlgrenska Uni6ersity Hospital, S-413 45 Go¨teborg, Sweden Received 7 April 2000; received in revised form 27 April 2000; accepted 14 September 2000

Abstract Aim: To describe the characteristics and outcome among patients suffering from an in-hospital cardiac arrest in women and men. Methods: All patients who suffered an in-hospital cardiac arrest during a 4 year period in Sahlgrenska Hospital Go¨teborg, Sweden, where the cardiopulmonary resuscitation (CPR) team was called, were recorded and described prospectively in terms of characteristics and outcome. Results: There were 557 patients suffering in-hospital cardiac arrest in whom the CPR-team was alerted. Among them, 217 (39%) were women. Women differed from men having a lower prevalence of earlier myocardial infarction, angina pectoris, renal disease and a higher prevalence of rheumatic disease. In terms of aetiology of the cardiac arrest, 47% men and 48% women were judged to have had a confirmed or possible AMI. More men than women were found in ventricular fibrillation/ventricular tachycardia (VF/VT) (57 vs. 41%; PB 0.001), whereas more women were found in pulseless electrical activity (30 vs. 15%; PB0.0001). Cerebral performance categories (CPC)-score at discharge did not differ between men and women. Among women, 36.4% survived to discharge as compared with 38.0% among men (NS). Survival from VF/VT was 64.3% in women and 52.7% in men (NS). When correcting for dissimilarities at baseline, the adjusted odd ratio for being discharged alive from hospital among women as compared with men was 1.66 (95% confidence limit 1.06– 2.62; P =0.028). Conclusion: Thirty nine percent of patients suffering in-hospital cardiac arrest for whom the CPR-team was alerted, were women. Women were less frequently found in VF/VT than men. After correcting for dissimilarities at baseline, female gender was associated with a small improvement in survival. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Cardiac arrest; In-hospital; Sex; Prognosis

Resumo Objecti6o: descrever as caracterı´sticas e resultados das paragens cardı´acas intra-hospitalares em homens e mulheres. Me´todo: registaram-se e descreveram-se prospectivamente todos os casos de paragem cardı´aca intra-hospitalar, para os quais fois chamada a equipa de reanimac¸a˜o, durante um perı´odo de 4 anos no Hospital Sahlgrenska em Gotemburgo. Resultados: a equipa de reanimac¸a˜o foi chamada para 557 doentes que tiveram paragem ca´rdio respirato´ria (PCR). Destes 217 (39%) eram mulheres. As mulheres distinguiram-se dos homens por terem uma menor prevaleˆncia de enfarte do mioca´rdio precoce, angina de peito, e doenc¸a renal e uma maior prevaleˆncia de doenc¸as reuma´ticas. Em termos etiolo´gicos 47% dos homens e 48% das mulheres foram classificados como tendo enfarte do mioca´rdio confirmado ou possı´vel. Foram encontrados em fibrilhac¸a˜o ventricular/taquicardia ventricular (FV/TV) sem pulso mais homens do que mulheres (57 vs 41%; PB 0.001) ao passo que havia mais mulheres em actividade ele´ctrica sem pulso (30 vs 15%, PB 0.001). As classificac¸a˜o do desempenho cerebral (CDC) a´ data da alta na˜o diferiu ´ data da alta 36.4% das mulheres e 38% dos homens (na˜o significativo) tinham sobrevivido. A ´ FV/TV entre homens e mulheres. A sobreviveram 64.3% das mulheres e 52.7% dos homens. Feitas as correcc¸o˜es para o estadio base, a ‘‘odd ratio’’ ajustada para sobrevida a´ data da alta das mulheres em comparac¸a˜o com os homens era de 1.66 (limites de confianc¸a de 95% 1.06–2.62, P= 0.028). Conclusa˜o: Dos doentes com paragem ca´rdio-respirato´ria para os quais foi activada a equipa de reanimac¸a˜o 39% eram mulheres. As mulheres tiveram menos FV/TV do que os homens. Feitas que foram as correcc¸o˜es para a situac¸a˜o basal, as mulheres tiveram uma sobrevida ligeiramente melhor. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Pala6ras cha6e: Paragem cardı´aca; Intra-hospitalar; Sexo; Progno´stico * Corresponding author. Tel.: + 46-31-3421000; fax: + 46-31-829650. E-mail address: [email protected] (J. Herlitz). 0300-9572/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 0 0 - 9 5 7 2 ( 0 0 ) 0 0 3 4 2 - 7

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1. Introduction During recent years, there has been an increased interest in the characteristics and outcome among patients suffering from in-hospital cardiac arrest [1–3]. Our earlier work has shown a relatively high chance of survival after in-hospital cardiac arrest [4]. A large proportion of in-hospital cardiac arrests are caused by an ischaemic event. Many earlier studies have highlighted the differences between men and women in terms of characteristics and outcome, when suffering from an ischaemic event [5 –9]. This study compares men and women in terms of characteristics and outcome, when suffering from an in-hospital cardiac arrest. The hypothesis was that they differed in terms of age, earlier history, initial arrhythmia and rate of survival.

seizures, ataxia, dysarthria, dysphasia or permanent memory or mental changes. 3. Patients with severe cerebral disability were conscious but dependent on others for daily support because of impaired brain function (in an institution or at home with exceptional family effort), and had at least limited cognition. This category included a wide range of cerebral abnormalities, from ambulatory with severe memory disturbance, through dementia precluding independent existence to paralytic and able to communicate only with eyes, as in the ‘locked-in’ syndrome. 4. Patients in a coma or vegetative state who were not conscious, unaware of their surroundings were not cognitive. They had no verbal or psychological interactions with their environment. 5. Patients who had a certified brain-death or were dead by traditional criteria.

2. Patients and methods

2.1. Organisation Between November 1, 1994 and December 31, 1998, all patients suffering from a suspected cardiac arrest where the cardiopulmonary resuscitation (CPR) team was called, were evaluated prospectively. Patients in whom the suspected arrest occurred either prior to hospital admission or in the emergency room were excluded. For each case, one case record form was filled in by the cardiologist in the CPR team and one by a nurse on the ward, where the arrest took place. Further clinical data were collected, retrospectively, based on information from medical records. The survivors functional status according to the cerebral performance category (CPC)-score [10] was evaluated, retrospectively, from the patients medical records, both on admission to, and at discharge from, hospital. The CPC-score was defined as follows — 1. Patients with a good cerebral performance, were conscious, alert, able to work and live a normal life, perhaps with minor psychological or neurological deficits (mild dysphasia, nonincapacitating hemiparesis or minor cranial nerve abnormalities). 2. Patients with moderate cerebral disability, were conscious and had sufficient cerebral function for part-time work in a sheltered environment or independent activities of daily life (dressing, travelling by public transport-sport, and preparing food), perhaps with hemiplegia,

At Sahlgrenska Hospital, there are 80 wards and 1980 beds. The hospital includes all specialities with exception of pediatrics and infectious diseases. In Fig. 1 is shown the distribution of all men and women admitted to the hospital during 1 year in relation to age (1996). The number of annual admissions was 57 805 and the number of annual deaths was 999 in 1996. Thus, the CPR team was alerted in 12.7% of all cardiac arrests in-hospital. Since 1966, there has been a resuscitation service, which has responded to cardiac arrest calls all over

Fig. 1. Distribution of patients admitted to hospital in relation to age.

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Table 1 Earlier history Women (N =217)

Men (N = 340)

Age (years) (3, 5)a Mean9 S.D.

709 15

69914

Earlier history (%) Bronchial asthma (0, 1) Cardiac arrest (0, 1) Myocardial infarction (0, 1) Angina pectoris (1, 2) Hypertension (3, 2) Diabetes (0, 1) Congestive heart failure (0, 3) Stroke (0, 2) Smoking (18, 29) Chronic alcohol abuse (1, 2) Cancer (0, 1) Renal disease (0, 1) Rheumatic disease (0, 1) Valvular heart disease (0, 2)

13 3 25 39 38 21 29 12 15 2 13 6 6 18

9 4 42 50 33 18 31 14 21 4 11 13 2 15

a

P

B0.0001 0.021

0.013 0.031

Number of patients in whom information is missing.

the hospital. This means that, when a cardiac arrest occurs, the hospital staff dial a specific number and a CPR-team consisting of a cardiologist, an anaesthesiologist and an internal medicine physician is immediately alerted. On each ward, there is an emergency kit including oxygen, suction devices, protective masks for mouth-to-mouth ventilation and bag valve masks for hand ventilation. On each ward, 1–2 CPR instructors are responsible for training the staff in basic life support (BLS). Up to 1996, manual defibrillators were stationed (available) on all wards with critical care patients, e.g. intensive care, coronary care, high dependency units. The nurses at these wards were trained and delegated to perform defibrillation with a manual defibrillator independently. The remaining wards had a separate emergency service, where manual defibrillators could be sent for, to be used by the CPR team. During 1996, 16 semi-automated external defibrillators (SAEDs), without ECG-display, but with vocal instructions to guide the nurse through the resuscitation programme, were located near all non-monitored wards. One SAED was shared by six wards. The nurses in these, who had been trained and authorised to use these devices could defibrillate independently of the CPR team. These nurses are retrained in the use of the SAED once a year. (The remaining wards obtained their defibrillators from

strategic points through a special transport organisation). Since 1992, there has been an educational programme and a special resuscitation training room for BLS and advanced life support (ALS). The nurses, assistant nurses and physicians are educated systematically in this room by persons who are involved in the educational programme on a fulltime basis. They also supervise the effectiveness of resuscitation in terms of use of equipment and whether ALS skills are adequate.

2.2. Statistical methods In the correlation test, Pitman’s non parametric permutation test was used [11]. In the evaluation of proportions, Fisher’s exact test was used, which is a special form of Pitman’s test [12]. A P-value B0.05 was regarded as significant. Two-tailed tests were applied. Adjusted odds ratio was estimated using Cox regression analysis. For a patient who suffered from several cardiac arrests in-hospital, only the first episode was included in the analysis.

3. Results In all, there were 557 patients suffering in-hospital cardiac arrest for whom the CPR-team was alerted during the time of the survey. Among them,

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217 (39%) were women compared with men, in terms of characteristics and outcome.

3.1. Earlier history Women differed from men having a lower prevalence of earlier myocardial infarction, angina pectoris and renal disease and a higher prevalence of rheumatic disease (Table 1). No other difference was found between women and men. The mean number of co-existing diseases as listed in the table were 2.691.7 for men and 2.49 1.7 for women (NS)

3.2. Symptoms that brought patients to hospital There was no difference between women and men (Table 2).

3.3. Final diagnosis In this table, the first diagnosis being recorded on the discharge chart from hospital is shown (Table 3). No difference was found between women and men.

3.4. Aetiology of the cardiac arrest In a retrospective evaluation of the aetiology, it was found that 47% of men and 48% of women were judged to have had a confirmed or possible

Fig. 2. Etiology to cardiac arrest.

AMI, as the cause of the cardiac arrest (Fig. 2). There was no significant difference between women and men.

3.5. Aetiology or symptoms immediately prior to cardiac arrest No difference was found between sexes (Table 4). About half of the patients had symptoms of heart failure prior to the arrest. About 20% had symptoms of respiratory insufficiency. AV-conduction disturbances were found in 12%. Hypotension was observed in little more than 20%. Slightly more than 10% had bleeding prior to the arrest. Slightly less than 10% had a diagnosis of the malignancy.

Table 2 Symptoms that brought patients to hospital

Symptoms (%) Chest pain Dyspnea Syncope Abdominal pain Tiredness Nausea Headache Bleeding Other pain Elective hospitalisation for investigation Elective hospitalisation for operation Accident Prehospital cardiac arrest Infection/fever Unconscious Other

Women (N= 217)

Men (N = 340)

35 13 4 1 1 3 0.9 0.5 3 7 13 2 0.5 2 2 10

39 9 1 2 4 2 0.6 2 3 6 12 2 1 3 2 10

P

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Table 3 Final main diagnosis

Final diagnosis Myocardial infarction Angina pectoris Chest pain (other cause) Congestive heart failure Arrhythmia CABGa PTCAb Coronary angiography Other heart investigation Transitory cerebral ischemia attack Stroke Peripheral vessel disease Pulmonary embolism Infection Renal disease Diabetes Hypertension Chronic pulmonary disease Cancer Gastrointestinal bleeding Drug abuse Rheumatic disease (collagenosis) Other operation than CABG Accident (surgery) Accident (orthopedic) Other a b

Women (N=217)

Men (N=340)

27 9 0 7 7 3 3 3 0.5 0

28 9 0.9 7 7 4 3 3 0.6 0.3

2 3 1 6 2 0.5 0.5 1

3 2 0.6 4 1 0.3 0 0

6 0.5 1 0

4 2 0.9 0.6

6

3

0.9 2 8

1 1 11

Coronary artery bypass grafting. Percutaneous transluminal coronary angioplasty.

Fig. 3. First recorded rhythm at cardiac arrest.

Fig. 4. CPC-score at discharge.

min in men (NS). The mean interval between cardiac arrest and defibrillation among patients found in VF/VT was 3.694.1 min in women and 2.993.6 in men (NS).

3.9. Initial rhythm being recorded at cardiac arrest

Among women, 89% of the arrests were witnessed compared with 88% in men (NS).

Men were more frequently found in VF/VT than women (PB0.001) and women were more frequently found in pulseless electrical activity (PEA) (PB0.0001) (Fig. 3).

3.7. Type of ward where the arrest took place

3.10. Treatment of cardiac arrest

Among women, the arrest took place in a ward with monitoring facilities in 48% compared with 52% of the men (NS). 3.8. Delay in starting treatment

Among the patients found in PEA, men had more defibrillations (P=0.0003; mean of 1.0 for men vs. 0.14 for women). Men were also intubated more frequently (Table 5).

The mean interval between cardiac arrest and the call for the CPR-team was 1.49 2.0 (S.D.) min in women and 1.492.3 min in men (NS). The mean interval between cardiac arrest and start of BLS was 1.1 9 1.7 min in women and 1.092.1

3.11. CPC-score at discharge

3.6. Witnessed arrest

No difference was found between women and men with regard to CPC-score at discharge (Fig. 4).

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Table 4 Etiology or symptoms immediately prior to cardiac arrest Women (N= 217)

Men (N=340)

Killip class 1 2 3 4

54 37 4 5

50 37 4 5

Myocardial infarction (6, 3)

39

41

Respiratory insufficiency (1, 2) No Yes, not requiring respirator Yes, requiring respirator

81 14 5

77 17 6

Heart failure (2, 2)a

AV conduction disturbance (3, 9) No 88 AV block I 3 AV block II 3 AV block III, narrow 0.9 complexes AV block III, broad complexes 1 AV block III, uncertain 3

88 3 2 1 2 4

Bradycardia (0, 1) No Yes

85 15

89 11

Hypotension (0, 2) No Yes, no cardiogenic shock Yes, cardiogenic shock

76 18 6

76 18 6

Bleeding (2, 2) No Yes, not requiring transfusion Yes, requiring transfusion

85 4 12

85 5 10

Pneumonia (1, 2)

6

8

Septicaemia (1, 3)

4

6

Unconscious (1, 2)

8

9

89 6 4 0.5

91 5 3 0.6

Malignancy (1, 3) No Yes, without metastases Yes, with metastases Yes, with metastases and cachexia a

Number of patients in whom information is missing.

3.12. Sur6i6al Survival to discharge rates were 36.4% in women and 38.0% in men (NS). Survival rates in

patients found in VF/VT were 64.3% in women and 52.7% in men (NS) and in patients found in asystole, the corresponding figures were 28.1 and 21.5% (NS). Among patients found in PEA, the corresponding figures were 9.8 and 4.2% (NS). Thus, in all three arrhythmia groups, survival was higher in women than in men. When correcting for the initial arrhythmia, all of the factors in Table 1 and whether the patient was resuscitated in a monitored ward or not, the adjusted odds ratio for women being discharged alive from hospital compared with men was 1.66 (95% confidence limit 1.06–2.62; P=0.028).

3.13. Relationship between the inter6al from collapse to defibrillation and sur6i6al Among women found in VF/VT, 64% were defibrillated 53 min after collapse, compared with 74% of the men (NS). In women found in VF/VT defibrillated 53 min after collapse, 73.5% survived to discharge, versus 57.9% in those defibrillated \3 min after collapse (NS). Among men, the corresponding values were 60.7 and 31.0%, respectively (P =0.011).

3.14. Retrospecti6e e6aluation of the decision to start CPR In a retrospective evaluation by the cardiologists in the team, it was found that 10% of the women, it was judged to be unjustified to start CPR compared with 5% of the men (NS).

3.15. Proportion of cardiac arrests in which CPR was started During the period of the survey, 1990 women and 2381 men suffered from a cardiac arrest. The rescue team was alerted in 217 of cardiac arrests in women (10.9%) and 340 of cardiac arrests in men (14.2%) (PB0.0001).

4. Discussion A number of studies have reported sex differences in the frequency, management and natural history of coronary artery diseases. The overall incidence of sudden cardiac death is lower in women [13], as is the proportion of deaths associated with coronary artery disease which occur as

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Table 5 Treatmenta VF/VT Women (n=81) Number of defibrillations Mean 2.3 Intubation 38 Adrenaline 40 Atropine 34 Lidocaine 32 Bicarbonate 29 Amiodarone 6 Magnesium 16 a

P

Asystole

P

PEA

P

Men (n=180)

Women (n=57)

Men (n=74)

Women (n= 61)

Men (n= 48)

2.7 35 41 31 33 30 12 9

0.4 60 65 53 4 39 4 0

0.4 62 80 66 6 45 1 1

0.14 60 85 72 2 43 0 0

1.0 83 92 55 4 58 2 0

0.0003 0.022

Results given in percentages if not otherwise stated.

sudden cardiac death [13]. Women who present with acute myocardial infarction, cardiac arrest or sudden cardiac death are also less likely to have pre-existing coronary artery disease. Women suffering cardiac arrest have also been shown to be less likely to have ischaemia, as the primary cause of arrest and less likely to have had an earlier myocardial infarction [14,15]. This study describes the characteristics and outcome in women and men suffering from in-hospital cardiac arrest. It has to be clearly stated that there is a selection of patients who suffer in-hospital cardiac arrest, for whom the CPR-team is alerted in our hospital. The CPR-team is called in only about 15% of all patients, who die in the hospital. In the remaining patients, reasons vary, why it has been judged futile to initiate CPR. Although we have no detailed information, it can be assumed that the majority of patients, for whom the CPR-team was not called, suffered from a terminal disease. Do not resuscitate orders are in operation at our hospital, but we do not know, how frequently. It has also been reported that among patients suffering out-of-hospital cardiac arrest, in whom resuscitation efforts were attempted, women were older than men [16,17]. In this survey, we found no significant difference. It has earlier been reported that women suffering in-hospital cardiac arrest are older than men [14]. When compared with the situation outside hospital, there was a slight increase in age both among women and men [16]. An earlier history of ischaemic heart disease, defined as either myocardial infarction or angina pectoris, was less frequent in women than men. Since the aetiology of arrest appear to be similar in women and men, we have

no clear explanation of this observation. It is, however, in agreement with other studies evaluating women and men suffering from cardiac arrest and other manifestations of ischaemic heart disease [18]. Neither can we explain why renal disease was less frequent in women than men. It has been suggested that cardiac etiology in out-of-hospital cardiac arrest is less common in women than in men [16]. In this smaller series of patients suffering from in-hospital cardiac arrest, no such tendency was observed. It has been reported that in out-of-hospital cardiac arrest VF/VT is less frequently observed in women than in men [15– 17]. A similar observation was made in this series of patients. There is no clear explanation of this finding. In out-of-hospital cardiac arrest, it has been suggested that the difference might be because, underlying myocardial ischaemia is less frequent in women than in men [14,15]. A reduced prevalence of bystander CPR in women compared with men [16] was another explanation for the observation in out-of-hospital cardiac arrest. One other possible explanation is that, the interval between cardiac arrest and ECG recording was longer in women than in men. This interval was not measured in the present study. However, the time between cardiac arrest and the call for the CPRteam and the initiation of BLS did not differ between sexes. Many earlier studies have evaluated the use of medication in women and men after suffering from various manifestations of ischaemic heart disease [19– 21]. Some have suggested a sex difference — women being less aggressively treated than men [21]. Other studies have not confirmed such results [19]. We found no deviations in terms

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of use of medication in patients with asystole and PEA. An interesting observation, however, was that in patients found in PEA, defibrillation occurred significantly less often in women compared with men. This means that among men, PEA was converted to VF/VT more often. There is no clear explanation of this finding. Among patients found in PEA, women were less frequently intubated. This might be explained to some extent by their higher survival rate (quicker return of spontaneous circulation and, therefore, no requirement for intubation). Overall, survival was similar in women and men. However, when analysing patients found in each rhythm separately, survival tended to be higher in women. Furthermore, we found females to be associated with a higher chance of survival, when various dissimilarities at baseline were taken into account. However, in the adjusted odd ratio, we did not adjust for a somewhat longer delay in defibrillation in women. Our results should be related to experiences in patients suffering from out-of-hospital cardiac arrest, where female has been reported to be associated with a higher immediate, but not long term, survival [16,17,22,23]. However, due to relatively small sample size and a P-value close to 0.05, our results need to be confirmed in a larger series of patients. A possible mechanism behind our observation is a sex-related difference in terms of autonomic and hemodynamic response to abrupt coronary occlusion [24]. Vagal activation is more common in women than in men, and this might have a beneficial antiarrhythmic effect [24]. Our results should be compared with other surveys of in-hospital cardiac arrest with a similar sample size, where female sex did not appear as an independent predictor of survival [25]. Different selection of patients for resuscitation in women and men is possible, since the rescue team was alerted significantly more often in men than in women. Overall survival was higher in this study than in many earlier reports [1–3,26,27]. One contributing factor might be a higher proportion of patients being found in VF/VT compared with other studies [3,25]. Another might be that CPR was initiated in a low proportion of patients overall. As earlier reported, [4] a high proportion of survivors had a CPC-score of one at discharge from hospital. No difference was found between women and men.

4.1. Limitations

1. The study suffers from a relatively small sample size. This increases the risk of type-2 errors. Furthermore, due to the large number of Pvalues created, P-values just below 0.05 should be interpreted with caution. 2. Time intervals were estimated by nurses and were not based on synchronised watches.

5. Conclusion Among patients suffering in-hospital cardiac arrest, for whom the CPR-team was called, 39% were women. They differed from men by being less frequently found in VF/VT and more frequently found in PEA. When correcting for dissimilarities at baseline, female sex was associated with a higher chance of survival.

Acknowledgements This study was supported by grants from The Swedish Heart and Lung Foundation and The Laerdal Foundation, Norway.

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