Anand Krishnan

Prognostic factors in obstetric patients admitted to an Indian intensive care unit

Objectives:Obstetric patients form a significant proportion of intensive care unit admissions in countries like India, where maternal mortality is high (440 per 100,000 deliveries). We studied the diseases requiring intensive care and prognostic factors in obstetric patients. Design:Retrospective chart review. Acute Physiology and Chronic Health Evaluation (APACHE) II data were prospectively collected. Setting:Multidisciplinary intensive care unit of a public hospital in Mumbai, India. Patients:Women admitted during pregnancy or 6 wks post-partum during a 5-yr study period (1997–2001). Interventions:None. Measurements and Main Results:Four hundred fifty-three obstetric patients (age 25.5 ± 4.6 yrs [mean ± sd], mean gestational age 31 wks) were admitted (548 intensive care unit admissions per 100,000 deliveries), 138 with single organ failure and 152 with multiple organ failure. Ninety-eight women died (mortality rate 21.6%). Mortality was comparable in antepartum (n = 216) and postpartum (n = 247) admissions but increased with increasing number of organs affected. There were 236 fetal deaths (52%), of which 104 occurred before hospital admission. Median APACHE II score was 16 (interquartile range, 10–24), and standardized mortality ratio (observed deaths/predicted deaths) was 0.78. Compared with pregnant patients admitted with obstetric disorders (n = 313), those with medical diseases (n = 140) had significantly lower APACHE II scores (median 14 vs. 17) but higher observed mortality rate (28.6% vs. 18.5%; odds ratio, 1.76; 95% confidence interval, 1.08–2.87) and standardized mortality ratio (1.09 vs. 0.66). On multivariate analysis, increased mortality rate was associated with acute cardiovascular (odds ratio, 5.8), nervous system (odds ratio, 4.73) and respiratory (odds ratio, 12.9) failure, disseminated intravascular coagulation (odds ratio, 2.4), viral hepatitis (odds ratio, 5.8), intracranial hemorrhage (odds ratio, 5.4), absence of prenatal care (odds ratio, 1.94), and >24 hrs interval between onset of acute symptoms and intensive care unit admission (odds ratio, 2.3). Conclusions:Multiple organ failure is common in obstetric patients; mortality rate increases with increasing organ failure. APACHE II scores overpredict mortality rate. Standardized mortality ratio is lower in obstetric disorders than in medical disorders. Lack of prenatal care and delay in intensive care unit referral adversely affect outcome and are easily preventable.

Oropharyngeal cleansing with 0.2% chlorhexidine for prevention of nosocomial pneumonia in critically ill patients: an open label randomized trial with 0.01% potassium permanganate as control.

BACKGROUND Oral cleansing with chlorhexidine decreases the incidence of nosocomial pneumonia in patients after cardiac surgery. However, evidence of its benefit in ICU patients is conflicting. METHODS Patients admitted to the ICU of an Indian tertiary care teaching hospital were randomized to twice-daily oropharyngeal cleansing with 0.2% chlorhexidine or 0.01% potassium permanganate (control) solution. Effects on the incidence of nosocomial pneumonia during ICU stay (primary outcome) and length of ICU stay and in-hospital mortality (secondary outcomes) were studied. RESULTS Five hundred twelve patients were randomized to either the chlorhexidine group (n = 250) or the control group (n = 262). Of the 471 subjects who completed the protocol, nosocomial pneumonia developed in 16 of 224 subjects (7.1%) in the chlorhexidine group and 19 of 247 subjects (7.7%) in the control group (p = 0.82; relative risk, 0.93; 95% confidence interval, 0.49 to 1.76); intention-to-treat analysis of 21 patients in whom the cleansing protocol was not followed revealed similar results. There was no significant difference between the study and control groups in the median day of development of pneumonia (5.0 days: interquartile range [IQR], 3.0 to 7.7 vs 5.0 days: IQR, 3.0 to 6.0, respectively), median ICU stay (5.0 days: IQR, 3.0 to 8.0 vs 6.0 days: IQR, 3.0 to 8.0, respectively), and mortality (34.8% vs 28.3%, respectively). On subgroup analysis, there was no significant difference in the primary and secondary outcomes in patients on mechanical ventilation, tracheal intubation, and coma (Glasgow coma scale <or= 8). During the study period, nosocomial pneumonia developed in fewer subjects (35 of 471 subjects [7.4%]) than in the 3 months preceding and following the study (98 of 452 subjects [21.7%]; p < 0.001; relative risk, 0.34; 95% confidence interval, 0.24 to 0.49). CONCLUSIONS Oropharyngeal cleansing with 0.2% chlorhexidine solution was not superior to oral cleansing with the control solution. However, the decreased incidence of nosocomial pneumonia during the study period suggests a possible benefit of meticulous oral hygiene in ICU patients.

Severe falciparum malaria: An important cause of multiple organ failure in Indian intensive care unit patients

ObjectiveTo study the incidence and severity of multiple organ dysfunction in severe falciparum malaria. DesignProspective, observational study. SettingIntensive care unit of a tertiary care university hospital. PatientsThree hundred one consecutive patients with severe falciparum malaria admitted during the 30-month study period. InterventionsDaily assessment of clinical and biochemical variables required for calculating the Sequential Organ Failure Assessment (SOFA) score. Measurements and Main ResultsCentral nervous system failure was present in 121 patients (53 deaths). Renal failure occurred in 91 patients (48 deaths), and 33 required dialysis. Severe thrombocytopenia occurred in 114 patients (seven required platelet transfusion), and 19 patients had thrombocytopenia and disseminated intravascular coagulation; all required component therapy; 229 patients received blood transfusion for severe hemolytic anemia. Hepatic failure occurred in 77 patients (38 deaths). Respiratory failure developed in 79 patients and carried the worst outcome (70 deaths). It occurred later in the course of the illness (mean, 3.1 days; p < .001) compared with cerebral, renal, and coagulation failure (mean, 1.3–2.3 days). Regardless of the organ system involved, only 11 of 172 patients with one or no organ failure died (6.8%), whereas mortality rate increased to 48.8% in 129 patients with multiple organ failure. Other abnormalities associated with poor outcome included seizures in 54 patients (56% mortality rate), metabolic acidosis in 167 (40% mortality rate), hypoglycemia in 88 (39% mortality rate), and hemoglobinuria in 190 (33% mortality rate). Sixty patients had quinine toxicity requiring dosage reduction. Bacterial sepsis occurred in 39 patients (35 deaths) and accounted for 85% of deaths occurring after day 7. Twenty-three pregnant women had no significant difference in outcomes. Overall mortality rate was 24.6% (301 patients, 74 deaths). ConclusionsMalaria is an important cause of multiple organ failure in India. Mortality rate is 6.4% when one or fewer organs fail but increases to 48.8% with failure of two or more organs. However, outcomes are better than for similar degrees of organ failure in sepsis.

Cavernous sinus thrombosis and meningitis from community-acquired methicillin-resistant Staphylococcus aureus infection

Septic cavernous sinus thrombosis is an uncommon clinical syndrome with a high morbidity and mortality. The commonest bacterial pathogen is Staphylococcus aureus. We describe the study of a patient with cavernous sinus thrombosis and meningitis caused by community‐acquired methicillin‐resistant S. aureus (CA‐MRSA) infection. The isolate was genotyped as the ST93 (Queensland) clone of CA‐MRSA and carried the Panton‐Valentine leucocidin genes. Cure was obtained following prolonged antimicrobial therapy with vancomycin, rifampicin, cotrimoxazole and linezolid. Given the high morbidity and mortality of cavernous sinus thrombosis and the worldwide recent emergence of CA‐MRSA, clinicians treating patients with this infection should consider early empirical coverage for CA‐MRSA with an antimicrobial agent, such as vancomycin or linezolid, particularly in the presence of suspected facial staphylococcal skin infections. If vancomycin is used, we emphasize that high doses may be required to achieve even low levels in the cerebrospinal fluid.

Cerebral venous and dural sinus thrombosis in severe falciparum malaria

Common causes of coma in falciparum malaria are cerebral malaria, hypoglycaemia and electrolyte disturbances. Focal deficits due to arterial infarcts may sometimes occur in children, but are rare in adults. Three adults with falciparum malaria who had fever, altered consciousness and focal neurological deficits (one of whom also had seizures) are being reported here. CT scan of the brain revealed haemorrhagic infarction of the cerebral cortex and subcortical white matter with surrounding oedema suggestive of venous infarction in all three patients. The diagnosis of cerebral venous thrombosis was missed in the first patient, and was detected only at autopsy. In the next two patients, superior sagittal sinus thrombosis was confirmed angiographically. Only one patient survived; the other two died of increased intracranial pressure. Two of the three patients also had Plasmodium vivax co-infection. A hypercoagulable state resulting from severe malaria may be responsible for this rare and potentially fatal complication. Cerebral malaria may be associated with raised intracranial pressure due to cerebral oedema. Cerebral venous thrombosis may worsen this and adversely affect outcome. This diagnosis should be suspected in patients with severe malaria who develop focal neurological deficits and confirmed by appropriate imaging; judicious use of local thrombolytic therapy may help improve outcome.

Scurvy: Historically a plague of the sailor that remains a consideration in the modern intensive care unit

We report the case of the case of a 56 year old female with sepsis on a background of rheumatoid arthritis and steroid use manifesting with overt clinical features of scurvy. Ascorbic acid assays were able to demonstrate severe deficiency and confirm a diagnosis of scurvy. Clinical resolution of signs and symptoms following commencement of vitamin C replacement was rapid. The intensivist and dietitian need to consider this diagnosis even in the first world setting, particularly in the presence of sepsis, inflammatory conditions, steroid use and importantly malnutrition.

Benzathine penicillin, metronidazole and benzyl penicillin in the treatment of tetanus: a randomized, controlled trial

Abstract Penicillin, the drug of choice in tetanus, may potentiate the effect of tetanus toxin by inhibiting the type-A (GABAA) receptor for γ-amino-n-butyric acid. Metronidazole has therefore been suggested as an alternative. Intramuscular benzathine penicillin (1.2 million units as a single dose; N = 56), enteral metronidazole (600 mg every 6 h for 10 days; N = 55) and intravenous benzyl penicillin (2 million units every 4 h for 10 days; N = 50) were therefore compared, in a randomized, controlled trial, among patients with all grades of tetanus. On presentation, the three treatment groups were similar in terms of age and sex distributions, immune statuses, durations of illness, and their APACHE-II scores and Abletts grades of tetanus. Of the patients given benzathine penicillin, 36 required tracheostomy, 10 neuromuscular blockade, and 23 mechanical ventilation; the corresponding numbers for the metronidazole (34, 12 and 18, respectively) and benzyl-penicillin groups (39, 12 and 25, respectively) were similar (P > 0.10). The incidences of dysautonomia and nosocomial pneumonia and the numbers of in-hospital deaths (26 with benzathine penicillin, 19 with metronidazole and 22 with benzyl penicillin; P = 0.392) were also similar in each treatment arm. The length of the hospital stay was longer in the patients receiving benzyl penicillin than in the benzathine-penicillin or metronidazole groups, with means (S.D.) of 21.9 (15), 16.9 (11) and 19.9 (15) days, respectively, but the difference was not statistically significant (P = 0.09). Although the three antibiotic regimens investigated appear equally effective, benzathine penicillin offers the convenience of a single, intramuscular injection instead of the 10 days of therapy needed with the other two drugs.

Vitamin D measurement in the intensive care unit: methodology, clinical relevance and interpretation of a random value

Vitamin D deficiency, as measured by a random level of 25-hydroxyvitamin D is very prevalent in critically ill patients admitted to the ICU and is associated with adverse outcomes. Both 25(OH)vitamin D and 1α,25(OH)2D3 are difficult to analyse because of their lipophilic nature, affinity for VDBP and small concentrations. Also, the various tests used to estimate vitamin D levels show significant inter- and intra-assay variability, which significantly affect the veracity of the results obtained and confound their interpretation. The two main types of assays include those that directly estimate vitamin D levels (HPLC, LC-MS/MS) and competitive binding assays (RIA, EIA). The former methods require skilled operators, with prolonged assay times and increased cost, whereas the latter are cheaper and easy to perform, but with decreased accuracy. The direct assays are not affected by lipophilic substances in plasma and heterophile antibodies, but may overestimate vitamin D levels by measuring the 3-epimers. These problems can be eliminated by adequate standardization of the test using SRMs provided by NIST, as well as participating in proficiency schemes like DEQAS. It is therefore important to consider the test employed as well as laboratory quality control, while interpreting vitamin D results. A single random measurement may not be reflective of the vitamin D status in ICU patients because of changes with fluid administration, and intra-day variation in 25-hydroxyvitamin D levels. 1α,25(OH)2D3 may behave differently to 25-hydroxyvitamin D, both in plasma and at tissue level, in inflammatory states. Measurement of tissue 1α,25(OH)2D3 levels may provide the true estimate of vitamin D activity.

Vitamin D in Critical Illness

Vitamin D is well known for its regulatory effects on calcium and phosphate homeostasis and its role in the maintenance of bone integrity. Over the past decade, there have been data from biochemical and molecular genetic studies that point to vitamin D having a much wider role than just maintenance of calcium and phosphate metabolism. Vitamin D and its synthetic analogues have been shown to have anticancer properties as well as to modulate the immune system. Recently, vitamin D deficiency has been reported in critically ill patients [1, 2]. However, it is still unclear how this deficiency affects patient outcomes in intensive care. The focus of this chapter is to examine the role of vitamin D in the body, with discussion of its effects on mineral and bone metabolism as well as its pleiotropic effects and the role it may play in the pathophysiology of critical illness.