Patients With Hematological Disorders Requiring Admission To Medical Intensive Care Unit In A Developing Country: Characteristics, Survival And Prognostic Factors
H Subhash, B George, A Devi, G John, M Chandy, A Srivastava
hematological disorder, icu, mechanical ventilation, prognosis
H Subhash, B George, A Devi, G John, M Chandy, A Srivastava. Patients With Hematological Disorders Requiring Admission To Medical Intensive Care Unit In A Developing Country: Characteristics, Survival And Prognostic Factors. The Internet Journal of Emergency and Intensive Care Medicine. 2003 Volume 7 Number 2.
This retrospective study assessed the characteristics and outcome of patients with hematological disorders who required admission to medical intensive care unit over a 4 year period from January 1998 to December 2001. 104 patients were studied, 67 (64%) males and 37 (36%) females with a mean age of 36.3 ± 15.3 (10 to 65) years. Common indications for ICU admission included respiratory distress in 56%, hemodynamic instability in 24% and poor sensorium in 20%. Forty-three (42%) patients had ANC
<500/mm3 while 48 (47.5%) had Platelet counts < 20,000/mm3. Mean duration of ICU stay was 4 days (< 24 hours to 28 days). Sixty-nine (66%) patients required mechanical ventilation while 61 (59%) required hemodynamic support. Twenty-five (24%) survived ICU stay and 20 (19%) survived to hospital discharge. ICU admission following cardio-pulmonary arrest, requirement of mechanical ventilation, vasopressor support, ANC count < 500/mm3 and platelet count < 20000/mm3 were predictors of an adverse outcome.
Hematological disorders are increasingly being treated over the past two decades in developing countries. Advances in the therapeutic modalities have considerably improved the prognosis in these patients and complete cure can be achieved in a considerable number of patients with hematological disorders1,2,3. However these patients are highly susceptible to overwhelming infections particularly during the period of severe neutropenia. Haemorrhagic complications secondary to severe thrombocytopenia are also common in these patients. It is inevitable that some of these complications may require a multidisciplinary approach and may necessitate intensive care management (ICU), particularly the need for mechanical ventilation and haemodynamic support. The outcome of patients with hematological malignancies requiring ICU care are known to be very poor, but in some patients intensive care management can be life saving4,5,6,7,8,9,10,11,12. This study was conduced with a view to assess the utility and outcome of patients with hematological disorders requiring ICU in a tertiary care center.
This retrospective study was conducted at the Christian Medical College & Hospital, a tertiary care 1800-bed university teaching hospital in south India. By reviewing admission records, we identified all patients who were admitted to the Medical intensive care unit with various hematological disorders between January 1998 through December 2001. Information was collected by reviewing the medical records on the demographic characteristics, underlying hematological conditions, indications for ICU admission and duration of ICU stay. The need for various supportive measures (mechanical ventilatory support, hemodynamic support and various other therapeutic interventions) were ascertained. The SOFA (sepsis-related organ failure assessment scoring system) was used to determine the organ dysfunction in these patients during the first 24 to 48 hours of ICU admission. In addition to the laboratory parameters required for the SOFA scoring, other laboratory results, arterial blood gas values, results of culture, biopsy specimens and autopsy reports were obtained when available.
Patients discharged from ICU and transferred back to the ward, regardless of subsequent outcome, were considered as
There were a total of 3070 hospital admissions with various hematological disorders during the period January 1998 to December 2001. One hundred and four (3.3%) of these patients required admission to the Medical ICU. During the same period there were a total of 3130 admissions to the Medical ICU and 104 (3.3%) of the ICU admissions were due to hematological disorders.
Demographic characteristics and underlying hematological conditions
There were 67 (64%) male subjects and 37 (36%) female subjects with a mean age of 36.3 ± 15.3 years (range 10 to 65 years). The various hematological diagnosis of the study subjects are given in Table 1. Four patients had undergone bone marrow transplantation in the past, two of them were for chronic myeloid leukemia and two for non-Hodgkins lymphoma. Among the 104 patients 2 were tested positive for HIV Elisa and 5 were HbsAg positive. Sixty (58%) patients had received cytotoxic drugs during the current hospital admission or in the immediate past.
The mean duration from hospital admission to ICU admission was 11 days (range < 24 hours to 59 days). The common indications for admission into the ICU included respiratory distress in 56%, hemodynamic instability in 24% and poor sensorium in 20%. Respiratory failure or respiratory distress was the commonest reason for ICU admission in 58 (56%) patients. The PaO2 / FiO2 ratio was <300 in 14 and < 200 in 39 patients. Hemodynamic instability with a systolic blood pressure < 90 mm Hg was seen in 38(36%) patients though this was the indication for admission into ICU in only 25 patients(24%). Twenty-two (21%) were admitted due to low sensorium (low GCS) including 5 (5%) who were admitted following generalized tonic clonic seizures. Twelve (11.5%) were admitted into ICU following a cardio pulmonary arrest.
Investigations and SOFA score
The initial mean PaO2 was 156 mm Hg ± 104. Forty-five patients had leukopenia with a total leukocyte count less than 3000/cu mm. The SOFA score for organ dysfunction is given in Table 2. The exact Glasgow coma scale (GCS) at admission was difficult to establish accurately in view of the use of sedation in intubated patients, hence GCS was not included in the assessment of neurological status in the SOFA scoring. Of the available data, 18 (17%) had score above 10. The base line investigations other than those included in the SOFA score are given in Table 3.
ICU supportive measures
A total of 69 (66%) required endotracheal intubation and mechanical ventilation. Forty-three patients required endotracheal intubation on immediate arrival to ICU or were transferred to ICU after intubation in the ward. A further 26 patients required endotracheal intubation and mechanical ventilation during their ICU stay. Fifty-seven (55%) patients required vasopressor drugs that included dopamine, dobutamine and adrenaline in appropriate combinations for hemodynamic instability. During the current hospital admission, 96 (92%) patients received broad-spectrum antibiotics, 49 (47%) subjects received intravenous anti fungal drugs, 12 (11%) received anti viral drugs and 6 (6%) patients were on anti-TB medication. Granulocyte colony stimulating factor (G-CSF) was administered in 23 (22%) patients. All patients received either blood or its components during stay in ICU.
Outcome in ICU and hospital
The mean duration of ICU stay was 4 days (range < 24 hours to 28 days). Twenty-five (24%) patients survived ICU stay, 73 (70%) patients died in the ICU and 6 (6 %) patients requested discharge against medical advice from the ICU. Out of the 25 patients who survived the ICU stay 20 (19%) patients survived till hospital discharge. Three patients died in the ward after transfer from ICU and two were discharged from the hospital against medical advice. During the period from January 1998 to December 2001 there were 3026 other admissions to the Medical ICU from various departments with an overall mortality of 30%.
Diagnosis of condition requiring ICU admission
The final diagnosis was established by utilizing the results of culture, biopsy specimens, autopsy study and relevant noninvasive procedures where applicable. Sepsis was diagnosed in 46 (44%) patients, of them 33 had evidence of bacteremia with the majority being due to gram negative organisms. Pneumonia was diagnosed in 21 (20%) patients and cerebrovascular events in 20 (19%) patients. Table 4 gives the diagnosis in the 104 patients requiring admission to ICU.
Sepsis including bacterial and fungal*
In 18 (17%) patients, autopsy studies were performed after taking consent from first-degree relatives. Six patients were found to have disseminated primary disease and one of the above also had intracranial bleed. Pulmonary hemorrhages were noted in 5 patients with tuberculosis with pulmonary hemorrhage, liver necrosis and intracranial bleed in 1 patient each. Other findings included pulmonary oedema, interstitial pneumonitis, fungal pneumonia (aspergillosis), pericardial effusion, fungal granuloma of the lung, infective endocarditis and diffuse consolidation of the lung each in 1 patient.
The prognostic factors and the final outcome were assessed comparing patients who survived till hospital discharge (20) against those who did not survive till hospital discharge (84). All the patients admitted to the ICU following a cardio-pulmonary arrest and those with advanced malignancy did not survive till hospital discharge. Other prognostic factors are given in Table 5.
Sepsis including bacterial and fungal*
The various ICU supportive measures in combination with lab parameters and organ dysfunction contributing to mortality in the non-survivors are given in Fig 1.
ANC = Absolute neutrophil count
There are published reports on the utility of ICU care and its outcome among patients with hematological disorders from the West4,5,6,7,8,9,10,11,12. However there is paucity of data from the developing countries regarding this aspect. In this study about 3% of the patients with hematological disorders have required admission to Medical ICU, of which 66% had hematological malignancies. The percentage of patients who were bone marrow transplant recipients were few unlike reports from the developed countries4,13,14. This may be because post bone marrow transplant recipients patients are generally managed in the transplant unit in the absence of the requirement for mechanical ventilation.
The most common reason for ICU admission was respiratory distress or respiratory failure. However many patients had a combination of hemodynamic instability (36%) or low GCS (21%) along with respiratory failure. Previous studies have shown similar results among patients who require ICU care with hematological disorders 4,6,10,13,15. Few studies have shown that ICU mortality is best predicted by the diagnosis of respiratory failure at admission4,6,8,11. In one of the above studies6, only 9 out of 50 patients (18%) admitted with respiratory failure survived to hospital discharge.
Hospital mortality rates have been reported to be high ranging from 69 – 80% when patients with haematological malignancies develop an acute illness of sufficient severity to warrant ICU admission7. It is noted that the expected mortality among patients with hematological disorders who require ICU care is considerably higher than the predicted mortality compared to those patients admitted with other diseases4,6,23. The survival to hospital discharge in this present study was 19% almost comparable to the reports from various centers from the developed countries ranging from 18 – 23%4,5,6,7,12. Tremblay
In the present study the need for mechanical ventilation was significantly associated with high mortality. Sixty-six out of the 69 patients who required mechanical ventilation did not survive to hospital discharge. Jackson
Cerebro-vascular event also contributed to significant number of ICU admission in this study. Majority of these were due to intracranial bleeds secondary to severe thrombocytopenia. Forty-eight patients had a platelet count less than 20000/mm3. Most patients admitted with cerebro-vascular event did not survive to hospital discharge, but this value did not attain statistical significance. Earlier reports had shown that thrombocytopenic patients in ICU generally have a poorer prognosis compared to non-thrombocytopenic patients20. Mortality in ICU among patients with severe neutropenia is noted to be high11. In the present study 67% of the patients had drug induced cytopenia and the mortality was significantly associated with an ANC count less than 500/mm3.
Earlier published reports have shown that the requirement of ICU supportive measures for organ dysfunction is significantly associated with mortality among patients with hematological disorders who require ICU care8,10,11. Available data from this present study show that the number of patients with significant organ dysfunction is less among the survivors compared to non-survivors, indicating poorer prognosis for those who are admitted with significant organ dysfunction. Studies from our center have shown that infection with Gram negative organisms and fungal infections are the most common among patients with hematological malignancy21,22,23 and in post transplant patients24. In this present study, presence of sepsis was associated with a high mortality. Positive microbiological identification of an organism did not improve the outcome compared with those patients who were diagnosed to have probable sepsis. A combination of mechanical ventilation, hemodynamic support, ANC count < 500/mm3 and platelet counts < 20000/mm3 were noted to be predictors of high mortality in those who did not survive to hospital discharge. The SOFA scoring system is shown to be useful in assessing organ dysfunction in ICU and studies have shown higher mortality in patients with higher scores15,25. We could not assess the neurological dysfunction by using this scoring system retrospectively. Our results indicate that SOFA score can be used with ease to assess the organ dysfunction, but the neurological dysfunction may be difficult to assess in view of sedation used in these patients.
We conclude that patients admitted following a cardio-pulmonary arrest, severe neutropenia with an ANC count < than 500/mm3, severe thrombocytopenia with a platelet counts < 20,000/mm3, patients requiring mechanical ventilatory and hemodynamic support have a poor prognosis in the ICU. The addition of other organ dysfunction further increases this mortality. The utility of non invasive ventilation among patients with hematological disorders need to be evaluated, to see if it could reduce the mortality as reported from other centers26,27,28.
Dr. Biju George Lecturer Dept of Haematology CMC Hospital Vellore – 632004 Tamil Nadu India Ph No: +91 – 0416 – 2222102 Ex 2352 Fax No: +91 – 0416 – 2232035/2232054 e-mail: firstname.lastname@example.org