Heat wave in Italy and hyperthermia syndrome.

Abstract: In the city of Modena, Italy, daily temperatures registered during the year 2003 showed a higher mean increase of 3[degrees] C compared with the previous three years, with average temperature of 26.1[degrees] C, compared with 22.8[degrees] C. The reported ambient temperature was higher than 32.3[degrees] C in 84% of the recorded days, and daily values exceeded 35.1[degrees] C in 62% of the days. During the summer, four heat waves occurred (June 11-15, July 21-23, August 3-15 and August 17-24).

Nine patients affected by hyperthermia syndrome with a mean body temperature of 41.4 [+ or -] 1.3[degrees] C were admitted to the Intensive Care Unit (ICU) of the Modena Teaching Hospital. Another patient with similar clinical features was not admitted to ICU, but to a general ward, and eventually died a few hours later. Mortality reached 80% and the mean survival time was 4.2 days with median values of one day. All patients except for one were admitted during one of the four above-mentioned heat waves, and in particular, 7 patients were admitted during the period from August 3rd to 15th. A common feature among 8 of the 10 patients was the chronic consumption of psychoactive drugs.

According to these observations, it is important to identify a population at risk in case of bioclimatological alarm, to find prevention strategies. It is extremely important in patients with hyperthermia to lower body temperature levels in the early hours to influence the malignant evolution of this severe pathologic process.

Key Words: hyperthermia, heat wave, psychoactive drugs

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Since the beginning of this century, the mean global environmental temperature has shown a steady and gradual increase. Several studies have outlined the effect of high ambient temperatures and high humidity on morbidity and mortality. (1-10)

The highest temperatures during the last 170 years were registered in the summer of 2003. In France, during the month of August, the Public Health Institute registered more than 14,800 deaths; approximately 60% higher than the average rate for that period of time. (11-13)

In the city of Modena, Italy, daily temperatures were registered with a mean increase of 3[degrees] C compared with the three previous years. During the summer of 2003, the average temperature was 26.1[degrees] C compared with 22.8[degrees] C during the period of reference. In 84% of the days, the highest temperature was above 32.3[degrees] C (90th percentile of the annual distribution of the observed values in the period 2000-2002) and in 62% of the days, daily values exceeded 35.1[degrees]C (95th percentile). Four heat waves occurred (June 11-15, July 21-23, August 3-15 and August 17-24). The first heat wave reached an average temperature of 37.6[degrees] C, the second 37.1[degrees] C. The third heat wave reached a mean value of 39.1[degrees] C, the hottest peak of the summer period, and the fourth wave had a mean value of 36.3[degrees] C.

Materials and Methods

Data for the retrospective observational study were obtained from the medical charts of patients admitted for hyperthermia to the ICU of the Modena Teaching Hospital in the summer of 2003. The article will mainly discuss the nine cases admitted to the ICU, while only initial data could be gathered on the 10th patient. Statistical analyses were conducted using the Statistical Program for Social Science (SPSS). Data were tested for normality using the Kolmogorov-Smirnov test. Continuous variables were reported as mean [+ or -] standard deviation. Normal variables, reported as rates, were compared through the [chi square] test or the Fisher's exact test when the number of observations in any one cell was less than five. Significance was set at P < 0.05.

Results

Nine patients affected by hyperthermia syndrome with a mean body temperature of 41.4 [+ or -] 1.3[degrees] C were admitted to the ICU of the Modena Teaching Hospital. Another patient with similar clinical features was not admitted to ICU, but to a general ward, and died a few hours later. Mortality reached 80%, and the mean survival time was 4.2 days with median values of one day. All patients except for one were admitted in the days belonging to one of the four above-mentioned heat waves and in particular, 7 patients were admitted during the period from August 3rd to 15th. The mean age of the sample (5 males, 5 females) was 56.4 [+ or -] 24.5 years. A common feature among 8 of 10 patients was the chronic consumption of psychoactive drugs. Two patients were taking drugs for psychosis and emotional problems, one was undergoing antiepileptic therapy, two patients used long half-life benzodiazepines as hypnotics and tranquilizers, one took selective serotonin reuptake inhibitors (SSRIs) and one patient was taking antiepileptic, anti-Parkinson and benzodiazepine medications. Eventually, of the two patients with negative pharmacological anamnesis, one was found to be a chronic alcoholic with an initial evolution toward hepatic cirrhosis, and one patient was elderly, overweight and with poor self-care conditions.

The association between the intake of psychoactive drugs and the onset of hyperthermia syndrome, featuring all patients admitted to the ICU of the Modena Teaching Hospital from June to September 2003, has been shown to be statistically significant (P <0.001). Nine patients were admitted in a state of coma with a Glasgow Coma Scale of 3/15 at the time of admission, and one patient presented with remarkable sensorium alterations, at which time pharmacological sedation was started. Brain CT scan, virological examinations and microbiologic examinations of blood, expectoration and urine samples were negative at the time of admission for all patients.

From a cardiocirculatory point of view, 7 patients showed severe hypotension at admission with a mean arterial pressure value of 57.5 mm/Hg and tachycardia (heart rate > 120 bpm). Two thirds of the patients had severe metabolic acidosis with base excess ranging from -7.2 to -16.4 at the first gas analysis. Eight patients underwent orotracheal intubation and mechanical ventilation with intermittent positive pressure ventilation modality (IPPV). Between the first and second day of ICU stay, renal failure started in all patients, resulting in the need for extrarenal hemofiltration for 3 of the 5 surviving patients during the first 48 hours. Eight patients developed massive hepatocytolysis in the first 72 hours, featured by peaks of transaminasemia 150 times higher than normal values. Statistical analysis of the patient's data showed a significant correlation (P = 0.015) between glutamate pyruvate transaminase (GPT) values and patient survival time. Coagulation deficits and hypoalbuminemia resulted in multiple plasma, albumin and platelet transfusions for 7 patients. Three patients, among the 5 who survived for longer than 2 days, developed progressive hemoglobinemia reduction, together with a platelet deficit and leukopenia with similar trends. These observations suggest that bone marrow damage may be included in the multiple organ failure which developed in these patients. Seven patients showed hyponatremia with natremia values of 127.1 [+ or -] 6.5 mEq/L (range 119-136). Body mass index (BMI) was calculated for 9 patients in the study, and we observed that, considering the variability induced by gender, 2 patients had Grade 1 obesity while the rest had Grade 2 obesity (mean BMI for males 32.3 [+ or -] 4.3; mean BMI for females 30.8 [+ or -] 2). (14)

There was a direct association between survival time and body temperature, both at admission and 24 hours after admission. Indeed the only 2 survivors, even with severe disabilities, showed a body temperature of 40[degrees] C and 40.5[degrees] C respectively at admission. Two days later, their body temperature decreased to 38[degrees] C with the use of cold crystalloid infusion and cooling systems. In 2 other patients, whose survival time ranged from 7 to 14 days, admission body temperature values were 41.5[degrees] C and 42[degrees] C, and decreased to 39[degrees] C and 40[degrees] C respectively on the second day. The remaining 5 patients had a mean body temperature at admission of 41.9 [+ or -] 1.3[degrees] C (range 40.8-43.5[degrees] C); only one of these patients survived the first 24 hours but died the following day with a body temperature higher than 41[degrees] C. Hence, we can infer the importance of immediate treatment to lower body temperature as rapidly as possible.

Discussion

The summer of 2003 represented an extreme meteorological event, but fortunately, this appears to have been an isolated occurrence. Indeed, during the summer of 2004, temperatures stayed within the ranges of seasonal normality, and ICU admission of patients with hyperthermia and progressive multiple organ failure did not occur. The preeminent feature of the sample examined is young age and consumption of psychoactive drugs, at least in eight cases. The consumption of these types of drugs is widely diffused throughout the standard population and is well known to trigger hyperthermia crisis. The coincidence of high environmental temperature and psychoactive drug consumption may have been a determinant in the origin of hyperthermia. (15,16)

Conclusion

According to these observations, it is important to identify a population at risk in case of bioclimatological alarm to find prevention strategies, such as drug dosage modification. Concerning treatment, it is extremely important in hyperthermic patients to lower body temperature levels in the early hours, to positively influence the malignant evolution of this severe pathologic process.

References

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I am only one, but I am one. I cannot do everything; but I will not let
what I cannot do interfere with what I can do.
--Edward Everette Hale

Alberto Barbieri, MD Cristina Pinna, MD, Luca Fruggeri, MD Emanuela Biagioni, MD and Anselmo Campagna, MD

From the Departments of Emergency and General Surgery and Surgical Specialities, University of Modena and Reggio Emilia, and Modena Teaching Hospital, Modena, Italy.

Reprint Requests to Alberto Barbieri, MD, Dipartimento di Emergenza-Urgenza, Universita degli Studi di Modena e Reggio Emilia, Policlinico, Via del Pozzo 71, 41100 Modena, Italy. Email: [e-mail]

Accepted April 10, 2006.

RELATED ARTICLE: Key Points

* At least 8 of the 10 patients in our study were taking psychoactive medications.

* Patients presented with hyperthermia and multiple organ failure.

* A high mortality rate was noted.