Why More Indians Die Of Sepsis Than Of Cancer

His family took him to Medanta Hospital where the treating doctor suspected that the young man--who had undergone surgery for a brain tumour in the previous year and was on chemotherapy and radiation therapy--had contracted a very severe infection in one of the hospitals he had frequently been in and out of.

“We immediately put him on the ventilator and ordered molecular testing of his respiratory secretions, which in a matter of hours, would help identify the infection and the medicines it would respond to,” Yatin Mehta, chairman, Institute of Critical Care and Anaesthesiology, Medanta - The Medicity Hospital, told IndiaSpend.

“We identified Klebsiella, a virulent bug, along with the medicine it would respond to, with which the patient started to recover and we were able to take him off the ventilator in three to four days,” said Mehta.

Sepsis is a life-threatening medical emergency occurring when the chemicals released in the bloodstream to fight an infection trigger inflammation throughout the body. The common symptoms of sepsis, as per the World Health Organization (WHO), are fever or hypothermia (below normal temperature), tachycardia (too fast a heart rate), rapid breathing, confusion and pain.

Sepsis caused one in five deaths globally in 2020, according to the WHO. Essentially, the world sees 11 million deaths due to sepsis annually, more than the 9.7 million people who died of cancer in 2022.

India’s sepsis burden is higher, at three in 10 deaths in 2017, according to the National Burden Estimates of healthy life lost in India and a study published in the journal CHEST. A better indicator of this burden is the sheer number of patients in intensive care units (ICUs) across the country with sepsis. In 2022, the George Institute for Global Health found that of 680 ICU patients across 35 ICUs, one in two ICU patients had sepsis, and 27.6% of those patients had died.

In 2023, the Kolkata branch of the Indian Society of Critical Care Medicine found that 30% of 224 patients admitted to ICUs in seven hospitals across the city had sepsis, exacerbating the condition they had been admitted for. Half had acquired sepsis during their hospital stay, while the other half had acquired it from the community.

A sepsis registry to collate India-specific, relevant data

While sepsis can occur as a result of an infection acquired from the community or from a hospital, “hospital-acquired infections are more difficult to treat, not just in India but globally”, said Mehta.

Essentially, “bugs found in the community tend to respond to simple antibiotics such as amoxicillin or ciprofloxacin while those found in hospitals tend to need a stronger medicine,” Mehta explained.

“Superbugs, irrespective of where they are found, can be resistant to multiple antibiotics (MDR), or extensive antibiotics (XDR) or even to every antibiotic available (PanDR).”

Keeping hospitals sterile and safe for patients necessitates optimal infection control practices, something every hospital has, but in varying degrees, continued Mehta. “You also need compliant doctors and clean indoor environments, but most public hospitals in India especially in the peripheries have sub-optimal infection control practices. They are understaffed and overcrowded.”

Experts from the Indian Council of Medical Research’s National Institute of Epidemiology writing in the Lancet in 2022 noted that many secondary or district-level health facilities in the public and private sectors have inadequate infection prevention and control measures.

Mehta underscored the need for data, something the WHO has also underlined. “Data is vital to solve this problem. The ICMR is coming out with some data but the Sepsis Forum of India has a new initiative to collate data too.”

Nineteen tertiary care institutions, both government-run and corporate-run, across India have come together to start a sepsis registry to share data on patients suffering from and succumbing to sepsis.

“A prospective pan India registry,” said Kapil Zirpe, head, Department of Neurocritical Care, Ruby Hall Clinic, Grant Medical Foundation, Pune, “will tell us which are the common organisms causing sepsis, what is the epidemiology of patients developing sepsis, what are the laboratory test parameters of patients with sepsis, what are the predictors of mortality in sepsis patients, what mortality rate are we seeing in sepsis patients and sepsis shock patients, and what factors affect the resistance pattern of organisms.”

A sepsis registry will also give us an opportunity to also understand the economic fallout of sepsis, added Kamini Walia, senior scientist and leader, Antimicrobial Resistance Initiative, Indian Council of Medical Research (ICMR). “A sepsis registry is a good initiative by the research fraternity of India. We need such data.”

A national sepsis registry would yield information on the difference in the prevalence of sepsis in rural and urban areas, and in private and public hospitals, said Dilip Bhanushali, president of the Indian Medical Association (IMA) and physician at the Udai Omni Hospital, Hyderabad.

Previously, we had data from individual centres or cities but a single centre or region cannot represent the larger population, said Zirpe, who is also president of the Sepsis Forum Society of India. By closing the gap on information about the Indian sepsis situation, the national registry would “open up many doors for understanding sepsis in India and how to screen for sepsis so that patients are picked up early and managed well”, he explained.

A sepsis registry will complement the information available with the government (ICMR), said Zirpe. “It would neither compete with nor replace any government initiative. Eventually, we hope that such initiatives will be started in government hospitals as well.”

Data will show who is more vulnerable to sepsis

In the absence of India-specific data, we have been extrapolating data from the West but that does not take cognisance of India’s unique challenges, said Saswati Sinha, senior consultant, Critical Care, Manipal Hospitals, Kolkata, and secretary of the Kolkata branch of the Indian Society of Critical Care Medicine. “The outcomes of a dataset unique to our country would be more reliable, they would guide us better.”

For instance, the WHO lists infants as well as the elderly, pregnant women, new mothers, hospitalised patients, patients in ICUs, people with weakened immune systems (such as due to cancer) and patients with chronic diseases as being more vulnerable to sepsis.

However, studies also show the susceptibility of other demographic groups. In a recently published sepsis study of 1,000 patients in south India, the median patient age was 55 and two in three patients were male. About half of these patients lived in villages and three in four were employed in the primary sector.

A study spanning Asian countries (India, Indonesia and Japan) showed that diabetes patients were more likely to develop sepsis than people with immunosuppression and malignancies, typical high risk groups in high income countries.

Diabetes (44%) and chronic renal failure (11.6%) were found to be the common comorbidities in the George Institute study of 680 patients admitted to 35 ICUs across the country, of whom more than half had sepsis.

“Comorbidities play a huge role in sepsis, by impacting how sepsis will progress and how a patient will respond to treatment,” said Sinha. “It doesn’t help that India is the diabetes capital of the world.”

Creating awareness of the epidemiology of patients who are more vulnerable to sepsis and their likely presentation could help its early detection, which Sinha called “the key to surviving sepsis”.

“In the peripheries where a lot of the patients we see come from, doctors fail to recognise that a patient is turning septic or already showing signs of sepsis, and therefore, they delay transferring the patient or giving the patient the care needed to increase the survival chances,” she said.

What the early data on sepsis patients tell us

An analysis of the first 1,172 patients’ data collated by the sepsis registry showed that the mortality of sepsis was higher (36.3%) than typical Western findings (around 20%) despite patients developing similarly severe symptoms. However, the mortality from septic shock (50.8%) was comparable to Western reports.

The average age of patients was 65 years, and 61% were male. Most patients had community-acquired infections, and the lung was the most common infected organ.

Klebsiella, Escherechia coli and Acinetobacter bacteria were among the predominant organisms, which is fairly typical. Bacteria are responsible for more sepsis cases than a virus or fungi. However, other experts have noted a rising contribution of viruses to sepsis.

Almost one in five patients had a viral cause of sepsis in a study of community-acquired sepsis in Kasturba Medical College, Manipal.

“Viruses are also known to cause sepsis,” explained Bala Venkatesh, Program Director, Critical Care, The George Institute for Global Health, “but not often thought about as a cause of sepsis.”

Venkatesh cited COVID-19 as a recent example where many of the manifestations would fit the diagnosis of a sepsis syndrome. “A severe form of dengue is another example of viral sepsis,” he said. With greater awareness, he added, more such cases will continue to get reported.

Irrational use of antimicrobials increasing sepsis cases

The WHO says the rational use of medicines requires that patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time, and at the lowest cost to them and their community.

In contrast, “the irrational use of medicine covers the failure to prescribe, dispense and use medicines as per guidelines; the use of too many medicines; the inappropriate use of antibacterials; their overuse where not required (such as self-medication); their underuse where required; their inadequate use for chronic diseases; and the use of expensive low-efficacy, low safety drugs,” explained Nilima Kshirsagar, former national chair, clinical pharmacology, ICMR.

The judicious or rational use of antimicrobials broadly means using stronger ones only when they are justified by the intensity of the patient’s symptoms, immunity level and the organism involved, said Ankur Gupta, consultant intensivist and founder president, Educational Society of Bedside Intensive Care Medicine, Indore.

Estimates showing that about half of the family spending on medicine in India is unnecessary point to the widespread irrational use of drugs. For instance, a 2021 survey of antimicrobial prescriptions of 1,747 admitted patients in tertiary care centres showed that drugs from the “Watch” category were most commonly prescribed. Close to half were on two or more antimicrobials. Only about one in five patients was prescribed drugs based on microbiology reports.

Watch medicines are only indicated for specific, limited number of infective syndromes, and are more prone to be a target of antibiotic resistance and thus prioritised as targets of stewardship programmes and monitoring, according to the WHO.

Irrational prescriptions can be traced to the insufficient training and awareness of medical professionals, which, in turn, can be traced to insufficient knowledge updates. A study of 506 medical professionals published in 2022 showed that theoretically, they understood antimicrobials but practically, many failed to identify the correct antimicrobial for a particular case. More than one third had not attended any continuing medical education on antimicrobials in the previous year.

Such irrational use “increases disease, mortality, adverse drug reactions, poor outcomes (whether disease cure or prevention), antimicrobial resistance and financial loss,” said Kshirsagar.

WHO literature shows that the irrational use of medicine has resulted in chloroquine-resistant falciparum malaria in 90% countries, 2-40% primary drug-resistant tuberculosis, and 10-90% ampicillin sulphamethoxazole / trimethoprim-resistant shigellosis.

Gupta pointed out that tuberculosis used to respond to streptomycin alone but then it grew resistant and needed a combination of medicines. “Organism mutation is an ongoing natural phenomenon that we have no control over,” he said. “So, the best way to prevent sepsis from becoming a non-treatable epidemic is to preserve the efficacy of the available arsenal of antimicrobials.”

Countering the malady of undertrained and unaware prescribers

In 2020, the ICMR launched a training programme in the rational use of antimicrobials, targeting registered general practitioners and interns who had just finished their training, said Kshirsagar.

Creating awareness of the role of antimicrobials in fighting infections and the right way of prescribing them is vital because in smaller hospitals and clinics and in the peripheries, the tendency is to choose a stronger antimicrobial than may be needed and sometimes, prescribe it in an inappropriate dosage, said Gupta.

The IMA has been conducting symposia and lectures across the country to educate doctors on the judicious use of antimicrobials. But quacks and alternative medicine (homeopathy, Ayurveda, Unani) practitioners also prescribe allopathic drugs including antimicrobials, which the government must stop, said Bhanushali.

“Unqualified doctors may tend to prescribe inappropriately high-end antibiotics,” he said. “We stand against this ‘mixopathy’, which is especially rampant in rural areas and smaller towns.”

Besides training, Kshirsagar said, we also need clinical guidelines for the rational use of medicines for different healthcare levels (primary, secondary and tertiary) and healthcare professionals (health workers, general practitioners and specialists) for common conditions and emergencies.

Allowing antibiotics to be available over the counter is another challenge, which “allows chemists to sell medicine without a prescription, which often happens irrationally,” added Gupta.

Challenges in antibiotic stewardship

The ICMR has also launched training programmes in antibiotic stewardship, the effort to measure and improve how antibiotics are prescribed by clinicians and used by patients.

Diagnostic stewardship and infection control practices must be in place to support antimicrobial stewardship, said Walia. “Diagnostic stewardship, in turn, needs a good lab and a microbiologist, and a good infection control team supported by a microbiologist and a nurse.”

The challenge is that in lower-tier hospitals, whether private or public sector, there is no investment in a good lab or a microbiologist, even on call, explained Walia. “Without these elements you cannot practice antibiotic stewardship and you will end up prescribing a broad spectrum cover to every patient because you don’t know what you are treating.”

That said, Walia pointed out that the unprecedented focus on district hospitals, through government investment, the ICMR’s revised National Essential Diagnostics List which mandates every district hospital to have a microbiologist and a well-functioning microbiology lab, and the conversion of many district hospitals into medical colleges (which must have a functional antibiotic stewardship committee as well as an infection control committee as per the National Medical Commission) augur well for antimicrobial resistance containment efforts and the sepsis challenge.

Walia also pointed out that some states are implementing the National Essential Diagnostics List through public-private partnerships, with the private partners providing the lab infrastructure, which is a start, although sustaining the initiative would require states to create their own lab infrastructure.

Creating mass awareness about sepsis

In 2012, the parents of Rory Staunton, a 12-year-old-boy living in New York, USA, who died of sepsis within days of a seemingly minor injury sustained during a game of basketball at school, spearheaded End Sepsis, a movement to create awareness of the number one killer disease of children in that country.

Rory’s story occurred in the USA but it could have happened anywhere in the world, more so in low and middle income countries which cumulatively account for 85% of the global burden of sepsis deaths.

Doctors cite low awareness among people as a big challenge in reducing sepsis cases and mortality. To create awareness of the rational use of medicines, “standard treatment guidelines should be publicised, promoted and easily available through the internet, mobile applications and printed version,” said Kshirsagar.

“It would be useful to develop patient information pamphlets for educating patients and society about the rational use of medicines. Product package inserts which are presently written for physicians should also be patient-oriented.”

In India, low awareness also means that people don’t turn to qualified health professionals when they first fall sick and instead, they try home remedies, said Bhanushali.

A delay in treating an infection can increase the chances of developing sepsis. Sinha said that the Covid-19 pandemic made people think that you can manage a low oxygen saturation case at home instead of escalating such cases immediately. She advocates a public campaign to create sepsis awareness. Among the top symptoms to look out for, she lists a fever which doesn't subside with the usual analgesics, abnormal behaviour or drowsiness, passing less urine, breathlessness, lethargy, cold extremities (hands and feet), and an evolving skin rash.

“These symptoms should trigger an alarm,” she says, “and the patient must be rushed to a higher centre.”

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