Sunday, October 30, 2016

Cracker waste clogs city drains.The Hindu Tiruchi 31.10 .2016

The Hindu
TIRUCHI, October 31, 2016

Cracker waste clogs city drains


Overnight rain had also compounded the problem to an extent
An eyesore:Garbage piled up near Angalamman Street in Tiruchi on Sunday.— Photo: B.Velankanni Raj

An eyesore:Garbage piled up near Angalamman Street in Tiruchi on Sunday.— Photo: B.Velankanni Raj

With the huge amount of festival waste, mainly burnt fire crackers strewn across, the Tiruchirappalli City Corporation is struggling to keep the city clean.

Garbage has been piled up in many places including Gandhi Market, a whole sale and retail vegetable market in the city, Big Bazaar, N.S.B. Road, Nandi Koil Street and Singarathope, where a number of commercial establishments are located, leading residential areas such as Thillai Nagar, Woraiyur, Cantonment, Palakkarai, Srirangam, Thiruvanaikoil and others. To make things worse, garbage bins were piled up with excess festival waste right from sweet boxes to plantain leaves and puja items.

Though the Corporation engages conservancy workers the very next day after Deepavali to clean the garbage, not many workers were seen on the streets on Sunday. It was said that the civic body could not employ sufficient workers as the next day of Deepavali happened to be a holiday this year. Moreover, the conservancy workers were yet to come out from the festive mood.

Overnight rain also compounded the problem to an extent. The flowing rain water had carried the garbage, particularly firecracker papers and plastics, to the drainage canals, chocking the free flow of drainage canals.

“Shopkeepers indiscriminately dump the waste on streets. The dust bins are overflowing for the last four days with excessive waste, making life difficult for the residents and shoppers,” says K. Venkaresan, a shop keeper at Angalamman temple on Big Bazaar street, pointing to an overflowing garbage bin.

Stressing the importance of expediting the cleaning operation, M.A. Aleem, former Vice Principal of K.A.P. Viswanatham Government Medical College, said that the meteorological department has predicted more rain for the next few days.

Hence, it was necessary to carry out cleaning work on a war footing. The entire waste generated during the festival season should be cleaned within a day. Clean and neat city would keep the citizens disease-free during the rainy season.


Crackers wastes clog city - The Hindu Tiruchi 31.10.2016

Friday, October 14, 2016

No Health care service without a Humanitarian Approach. Aleem M A . BMJ 2016;355:i5412


Refugee crisis presents a humanitarian paradox

BMJ 2016; 355 doi: (Published 10 October 2016)

Cite this as: BMJ 2016;355:i5412

Rapid response

Re: Refugee crisis presents a humanitarian paradox

No Health care service without a Humanitarian Approach.

Health care for refugees/migrants will definitely protect all the other people living in the country. Humanitarian approaches are the basis for each and every health professional in their day to day practices. So there won't be any neglect or discrimination dependent on the status of individuals by health professionals.

Competing interests: No competing interests

13 October 2016

M A Aleem


ABC Hospital

Annamalainagar Trichy 620018 Tamilnadu India


Tuesday, October 11, 2016

World Obesity Day 11.10.2016

World Obesity Day 11.10.2016
   - Dr. M A Aleem

World Obesity Day was launched in 2015 to stimulate and support practical solutions to help people achieve and maintain a healthy weight, and to reverse the obesity crisis. World Obesity Day 2016 shall focus on childhood obesity, aligning with the WHO Commision's report on Ending Childhood Obesity.

Child and adolescent obesity has risen rapidly around the world, with few countries taking action against this damaging health issue which affects later health, educational attainment and quality of life.

Facts on Obesity and overweight

Worldwide obesity has more than doubled since 1980.
In 2014, more than 1.9 billion adults, 18 years and older, were overweight. Of these over 600 million were obese.
39% of adults aged 18 years and over were overweight in 2014, and 13% were obese.
Most of the world's population live in countries where overweight and obesity kills more people than underweight.
41 million children under the age of 5 were overweight or obese in 2014.
Obesity is preventable.
What are overweight and obesity?

Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health.

Body mass index (BMI) is a simple index of weight-for-height that is commonly used to classify overweight and obesity in adults. It is defined as a person's weight in kilograms divided by the square of his height in meters (kg/m2).

For adults, WHO defines overweight and obesity as follows:

overweight is a BMI greater than or equal to 25; and
obesity is a BMI greater than or equal to 30.
BMI provides the most useful population-level measure of overweight and obesity as it is the same for both sexes and for all ages of adults. However, it should be considered a rough guide because it may not correspond to the same degree of fatness in different individuals.

For children, age needs to be considered when defining overweight and obesity.

Children under 5 years of age
For children under 5 years of age:

overweight is weight-for-height greater than 2 standard deviations above WHO Child Growth Standards median; and
obesity is weight-for-height greater than 3 standard deviations above the WHO Child Growth Standards median.
Charts and tables: WHO child growth standards for children aged under 5 years
Children aged between 5–19 years
Overweight and obesity are defined as follows for children aged between 5–19 years:

overweight is BMI-for-age greater than 1 standard deviation above the WHO Growth Reference median; and
obesity is greater than 2 standard deviations above the WHO Growth Reference median.
Charts and tables: WHO growth reference for children aged between 5–19 years
Facts about overweight and obesity

Some recent WHO global estimates follow.

In 2014, more than 1.9 billion adults aged 18 years and older were overweight. Of these over 600 million adults were obese.
Overall, about 13% of the world’s adult population (11% of men and 15% of women) were obese in 2014.
In 2014, 39% of adults aged 18 years and over (38% of men and 40% of women) were overweight.
The worldwide prevalence of obesity more than doubled between 1980 and 2014.
In 2014, an estimated 41 million children under the age of 5 years were overweight or obese. Once considered a high-income country problem, overweight and obesity are now on the rise in low- and middle-income countries, particularly in urban settings. In Africa, the number of children who are overweight or obese has nearly doubled from 5.4 million in 1990 to 10.6 million in 2014. Nearly half of the children under 5 who were overweight or obese in 2014 lived in Asia.

Overweight and obesity are linked to more deaths worldwide than underweight. Globally there are more people who are obese than underweight – this occurs in every region except parts of sub-Saharan Africa and Asia.

What causes obesity and overweight?

The fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories expended. Globally, there has been:

an increased intake of energy-dense foods that are high in fat; and
an increase in physical inactivity due to the increasingly sedentary nature of many forms of work, changing modes of transportation, and increasing urbanization.
Changes in dietary and physical activity patterns are often the result of environmental and societal changes associated with development and lack of supportive policies in sectors such as health, agriculture, transport, urban planning, environment, food processing, distribution, marketing, and education.

What are common health consequences of overweight and obesity?

Raised BMI is a major risk factor for noncommunicable diseases such as:

cardiovascular diseases (mainly heart disease and stroke), which were the leading cause of death in 2012;
musculoskeletal disorders (especially osteoarthritis – a highly disabling degenerative disease of the joints);
some cancers (including endometrial, breast, ovarian, prostate, liver, gallbladder, kidney, and colon).
The risk for these noncommunicable diseases increases, with increases in BMI.

Childhood obesity is associated with a higher chance of obesity, premature death and disability in adulthood. But in addition to increased future risks, obese children experience breathing difficulties, increased risk of fractures, hypertension, early markers of cardiovascular disease, insulin resistance and psychological effects.

Facing a double burden of disease

Many low- and middle-income countries are now facing a "double burden" of disease.

While these countries continue to deal with the problems of infectious diseases and undernutrition, they are also experiencing a rapid upsurge in noncommunicable disease risk factors such as obesity and overweight, particularly in urban settings.
It is not uncommon to find undernutrition and obesity co-existing within the same country, the same community and the same household.
Children in low- and middle-income countries are more vulnerable to inadequate pre-natal, infant, and young child nutrition. At the same time, these children are exposed to high-fat, high-sugar, high-salt, energy-dense, and micronutrient-poor foods, which tend to be lower in cost but also lower in nutrient quality. These dietary patterns, in conjunction with lower levels of physical activity, result in sharp increases in childhood obesity while undernutrition issues remain unsolved.

How can overweight and obesity be reduced?

Overweight and obesity, as well as their related noncommunicable diseases, are largely preventable. Supportive environments and communities are fundamental in shaping people’s choices, by making the choice of healthier foods and regular physical activity the easiest choice (the choice that is the most accessible, available and affordable), and therefore preventing overweight and obesity.

At the individual level, people can:

limit energy intake from total fats and sugars;
increase consumption of fruit and vegetables, as well as legumes, whole grains and nuts; and
engage in regular physical activity (60 minutes a day for children and 150 minutes spread through the week for adults).
Individual responsibility can only have its full effect where people have access to a healthy lifestyle. Therefore, at the societal level it is important to support individuals in following the recommendations above, through sustained implementation of evidence based and population based policies that make regular physical activity and healthier dietary choices available, affordable and easily accessible to everyone, particularly to the poorest individuals. An example of such a policy is a tax on sugar sweetened beverages.

The food industry can play a significant role in promoting healthy diets by:

reducing the fat, sugar and salt content of processed foods;
ensuring that healthy and nutritious choices are available and affordable to all consumers;
restricting marketing of foods high in sugars, salt and fats, especially those foods aimed at children and teenagers; and
ensuring the availability of healthy food choices and supporting regular physical activity practice in the workplace.

WHO response

Adopted by the World Health Assembly in 2004, the "WHO Global Strategy on Diet, Physical Activity and Health" describes the actions needed to support healthy diets and regular physical activity. The Strategy calls upon all stakeholders to take action at global, regional and local levels to improve diets and physical activity patterns at the population level.

The Political Declaration of the High Level Meeting of the United Nations General Assembly on the Prevention and Control of Noncommunicable Diseases of September 2011, recognizes the critical importance of reducing unhealthy diet and physical inactivity. The political declaration commits to advancing the implementation of the "WHO Global Strategy on Diet, Physical Activity and Health", including, where appropriate, through the introduction of policies and actions aimed at promoting healthy diets and increasing physical activity in the entire population.

WHO has also developed the "Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013-2020" which aims to achieve the commitments of the UN Political Declaration on Noncommunicable diseases (NCDs) which was endorsed by Heads of State and Government in September 2011. The “Global Action Plan” will contribute to progress on 9 global NCD targets to be attained by 2025, including a 25% relative reduction in premature mortality from NCDs by 2025 and a halt in the rise of global obesity to match the rates of 2010.

In 2016 the World Health Assembly welcomed the report of the Commission on Ending Childhood Obesity and its 6 recommendations to address the obesogenic environment and critical periods in the life course to tackle childhood obesity. The Assembly requested the Director-General to develop an implementation plan to guide further action.

*அம்மா*. உங்கள் வருகையை எதிர்பார்த்திருக்கும் கோடான கோடி இதயங்களில் நானும் ஒருவனாய்- டாக்டர். அலீம்

பூ போன்ற மகள்
அப்பல்லோவில் படுத்துக் கிடக்கிறாளே என
புலம்புதற்கு தாய் இல்லை....

நோய் தீர்ந்து என் மகள்
புன்னகை சிந்தி வருவாளென
பார்த்திருக்கத் தந்தை இல்லை...

தெய்வங்களைக் கேட்டே
என் சகோதரி நலம் மீட்பேன்
என்று பூசை செய்ய
சகோதரன் இல்லை..

மாற்றுடை வேண்டுமோ என
உடுப்புகள் தேடி எடுத்துப் போக
உடன் பிறந்த தங்கை இல்லை..

பெற்றவள் நலம் மீட்ட பின்பே
மற்ற வேலை என்று
மார் தட்டிச் சொல்வதற்கு மகன் இல்லை..

.மருந்து மாத்திரை தேடி
எடுத்து மணி தவறாமல்
மகள் இல்லை..

ஆனாலும் ஈரெட்டு நாட்களாய்
தாய் முகம் காணாமல்
எத்தனை இதயங்கள் இங்கே
கண்ணீரில் குளிக்கிறதே..
கட்டுக்கடங்கா கூட்டம்...
வாழ வைத்த தாய்
வாடிக் கிடக்கலாமோ என
செந்தனலில் இட்ட புழுவாய்

உள்ளங்கைக்குள் மாணவர்
உலகைக் காண மடிக்கணினி
தந்த மாதரசி நலம் பெறவே
வேண்டி நிற்கிறது மாணவச் சமூகம்..

காவேரியை மீட்டு வந்து
முல்லைப் பெரியாரை
காத்துத் தந்து கழனி வாழ்
உழவினத்தின் கண்ணீர் துடைத்த
எங்கள் கனிவு மனத் தாயுன் நிலை
பொறுக்காமல் உயிர் உருகும்
வேதனையில் உழவர் கூட்டம்
இன அழிப்பு இலஙகைக்குக்
குலைநடுக்கம் கொடுத்த
உலகத் தமிழினத்தின்
ஒப்பில்லாத் தலைவியை
ஒரு நோய் வந்து சாய்ப்பதுவா என
ஊணுறக்கம் கொள்ளலையே..

கருதரித்த பெண்ணுக்கு
ஒன்றிரண்டு பிள்ளை
கருணை தரித்த
எங்கள் அம்மா உமக்கோ
பத்து கோடி பாசப் பிள்ளைகள்..

வாஞ்சை மிகு தாய்
எழுந்து வரும் நாளை எதிர்பார்த்து வாடுதே  தமிழகம்  .....

*அம்மா*. உங்கள் வருகையை எதிர்பார்த்திருக்கும் கோடான கோடி இதயங்களில் நானும் ஒருவனாய்

Friday, October 7, 2016

Our climate is our planet. ALEEM M A . BMJ 2016;355:i5245


Healthcare professionals must lead on climate change

BMJ 2016; 355 doi: (Published 04 October 2016)

Cite this as: BMJ 2016;355:i5245

Rapid response

Our climate is our planet

Everyone has a responsibility to mitigate the consequences of climatic changes. We neurologists are very worried because many neurological diseases are influenced directly or indirectly by climatic changes.

To mitigate climatic changes, everyone in the health care system should plant green plants in and outside our hospitals, houses, and other work places. We should avoid plastics in our day to day life. We should use environmental friendly fuels. We must also help the proper disposal of biomedical and other hospital waste.

Competing interests: No competing interests

07 October 2016

M A Aleem


ABC Hosoital. Dhanalakshmi Srinivasan Medical College And Hosoital. Apollo Hospital.

Annamalainagar Trichy 620018. DSMCH Perambalur 621212. Apollo hospital Trichy 620010. Tamilnadu India

Evaluation and management of suspected sepsis and septic shock in adults

Evaluation and management of suspected sepsis and septic shock in adults

Gregory A Schmidt, MD

All topics are updated as new evidence becomes available and our peer review processis complete.

Literature review current through: Sep 2016. | This topic last updated: Sep 14, 2016.

INTRODUCTION — Sepsis is a clinical syndrome characterized by systemic inflammation due to infection. There is a continuum of severity ranging from sepsis to septic shock. Over 1,665,000 cases of sepsis occur in the United States each year, with a wide range in mortality, depending upon the population studied [1]. Even with optimal treatment, mortality from sepsis is estimated to be ≥10 percent and from septic shock is ≥40 percent [2].

In this topic review, the management of sepsis and septic shock is discussed. Definitions, diagnosis, pathophysiology, and investigational therapies for sepsis, as well as management of sepsis in the asplenic patient are reviewed separately. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis" and"Pathophysiology of sepsis" and"Investigational and ineffective therapies for sepsis" and "Clinical features and management of sepsis in the asplenic patient".)


The earlyadministration of fluids and antibiotics is the cornerstone of management for patients with sepsis and septic shock.

Therapeutic priorities for patients with sepsis or septic shock include:

●Early initiation of supportive care to correct physiologic abnormalities, such as hypoxemia and hypotension [3-7].

●Distinguishing sepsis from systemic inflammatory response syndrome (SIRS) (table 1) because, if an infection exists, it must be identified and treated as soon as possible (table 2). This may require appropriate antibiotics as well as a surgical procedure (eg, drainage).


The first priority in any patient with sepsis or septic shock is stabilization of their airway and breathing. Next, perfusion to the peripheral tissues should be restored and antibiotics administered [6,8].

Stabilize respiration — 

Supplemental oxygen should be supplied to all patients with sepsis and oxygenation should be monitored continuously with pulse oximetry. Intubation and mechanical ventilation may be required to support the increased work of breathing that typically accompanies sepsis, or for airway protection since encephalopathy and a depressed level of consciousness frequently complicate sepsis [9,10].

The choice and use of sedative and induction agents (eg, etomidate, ketamine) used to intubate patients with sepsis or septic shock are discussed separately. Other aspects of intubation and mechanical ventilation are similarly described elsewhere. (See "Induction agents for rapid sequence intubation in adults"and "Advanced emergency airway management in adults" and "Rapid sequence intubation for adults outside the operating room" and "The decision to intubate" and "The difficult airway in adults".)

Chest radiographs and arterial blood gas analysis should be obtained following initial stabilization. These studies are used in combination with other clinical parameters to diagnose acute respiratory distress syndrome (ARDS), which frequently complicates sepsis. (See "Acute respiratory distress syndrome: Clinical features and diagnosis in adults" and"Mechanical ventilation of adults in acute respiratory distress syndrome".)

Assess perfusion — 

Once the patient's respiratory status has been stabilized, the adequacy of perfusion should be assessed. Hypotension is the most common sign but critical hypoperfusion can also occur in the absence of hypotension, especially during early sepsis. Clinical signs of impaired perfusion include the following:

●Hypotension –

Hypotension is the most common indicator that perfusion is inadequate (eg, systolic blood pressure [SBP] <90 mmHg, mean arterial pressure <70 mmHg, decrease in SBP >40 mmHg). Therefore, it is important that the blood pressure be assessed early and often. Because a sphygmomanometer may be unreliable in hypotensive patients, an arterial catheter may be inserted if blood pressure is labile or restoration of arterial perfusion pressures is expected to be a protracted process [5]. Attempts to insert an arterial line should not delay the prompt management of shock. (See "Arterial catheterization techniques for invasive monitoring".)

●Signs of poor end-organ perfusion –

Warm, flushed skin may be present in the early phases of sepsis. As sepsis progresses to shock, the skin may become cool due to redirection of blood flow to core organs. Additional signs of hypoperfusion include tachycardia >90 per min, obtundation or restlessness, and oliguria or anuria.

These findings may be modified by preexisting disease or medications. As examples, older patients, diabetic patients, and patients who take beta-blockers may not exhibit an appropriate tachycardia as blood pressure falls. In contrast, younger patients frequently develop a severe and prolonged tachycardia and fail to become hypotensive until acute decompensation later occurs, often suddenly. Patients with chronic hypertension may develop critical hypoperfusion at a higher blood pressure than healthy patients (ie, relative hypotension).

●Elevated –

An elevated serum lactate (eg, >2 mmol/L) can be a manifestation of organ hypoperfusion in the presence or absence of hypotension and is an important component of the initial evaluation, since elevated lactate is associated with poor prognosis [6,11-13]. A serum lactate level ≥4 mmol/L is consistent with, but not diagnostic of, septic shock. Additional laboratory studies that help characterize the severity of sepsis include a low platelet count, and elevated international normalized ratio, creatinine, and bilirubin. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis", section on 'Septic shock'.)

●Other –

Tests that combine output from many organs (eg, arterial lactate) may obscure the presence of significant ischemia in an individual organ [14]. Gastric tonometry indirectly measures perfusion to the gut by estimating the gastric mucosal PCO2. It can be used to detect gut hypoxia by calculating the gastric to arterial PCO2 gap [14-16]. But, gastric tonometry is not widely available and it is uncertain whether it can successfully guide therapy. Additional studies and clinical experience are needed.

Establish venous access — 

Venous access should be established as soon as possible in patients with suspected sepsis. While peripheral venous access may be sufficient in some patients, particularly for initial resuscitation, the majority will require central venous access at some point during their course. A central venous catheter (CVC) can be used to infuse intravenous fluids, medications (particularly vasopressors), and blood products, as well as to draw blood for frequent laboratory studies. In addition, this access can be used for hemodynamic monitoring by measuring the central venous pressure (CVP) and the central venous oxyhemoglobin saturation (ScvO2). While in the past, a major purpose of a CVC was the measurement of ScVO2 and CVP, evidence from randomized trials on the value these targets to follow therapeutic effect is conflicting [17-19below and "Complications of central venous catheters and their prevention".)

We believe that pulmonary artery catheters (PACs) should not be used in the routine management of patients with severe sepsis or septic shock. PACs can measure the pulmonary artery occlusion pressure (PAOP) and mixed venous oxyhemoglobin saturation (SvO2). In theory, this may be helpful to guide circulatory resuscitation. However, the PAOP has proven to be a poor predictor of fluid responsiveness in sepsis and the SvO2 is similar to the ScvO2, which can be obtained from a CVC [20,21]. PACs increase complications and have not been shown to improve outcome [22-24]. (See"Pulmonary artery catheterization: Indications, contraindications, and complications in adults".)

Interventions to restore perfusion — 

The rapid restoration of perfusion is predominantly achieved by the administration of intravenous fluids, usually crystalloids. Modalities such as vasopressor therapy, inotropic therapy, and blood transfusion are added, depending on the response to fluid resuscitation, evidence for myocardial dysfunction, and presence of anemia. (See "Treatment of severe hypovolemia or hypovolemic shock in adults".)

Intravenous fluids — 

In patients with sepsis, intravascular hypovolemia is typical and may be severe, requiring rapid fluid resuscitation.

Volume — 

The optimal volume of resuscitative fluid is unknown. Several studies of early goal directed therapy reported intravenous fluid infusions targeted to physiologic endpoints and resulted in volumes ranging from 3 to 5 liters [17-19]. The volume of fluid that was administered within the initial six hours of presentation was targeted to set physiologic endpoints (eg, mean arterial pressure). While an early study of early goal-directed therapy (EGDT) reported mean infusion volume in the first six hours of 3 to 5 liters [17], later trials reporting mean infusion volumes of 2 to 3 liters [18,19]. Thus, rapid, large volume infusions of intravenous fluids are indicated as initial therapy for severe sepsis or septic shock, unless there is coexisting clinical or radiographic evidence of heart failure. Suggested targets for fluid resuscitation are discussed separately. (See 'Goals of initial resuscitation' below.)    

Fluid therapy should be administered in well-defined (eg, 500 mL), rapidly infused boluses [6]. Volume status, tissue perfusion, blood pressure, and the presence or absence of pulmonary edema must be assessed before and after each bolus. Intravenous fluid challenges can be repeated until blood pressure and tissue perfusion are acceptable, pulmonary edema ensues, or fluid fails to augment perfusion.

Careful monitoring is essential because patients with sepsis may develop noncardiogenic pulmonary edema (ie, acute respiratory distress syndrome [ARDS]). Once patients with ARDS have been fluid resuscitated a liberal approach to intravenous fluid administration has been shown to prolong the duration of mechanical ventilation, compared to a more restrictive approach that also typically requires large doses of furosemide [25]. In addition, small retrospective studies have reported that fluid overload is common in patients with sepsis and is associated with the increased performance of medical interventions (eg, diuresis, thoracentesis); the effect of fluid overload and such interventions on mortality and functional recovery is unclear [26-28]. Thus, while the early, aggressive fluid therapy is appropriate in sepsis and septic shock, fluids may be unhelpful or harmful when the circulation is no longer fluid-responsive. (See"Acute respiratory distress syndrome: Supportive care and oxygenation in adults", section on 'Fluid management'.)

Choice of fluid — 

Evidence from randomized trials and meta-analyses have found no convincing difference between using albumin solutions and crystalloid solutions (eg, normal saline, Ringer’s lactate) in the treatment of sepsis or septic shock, but they have identified potential harm from usingpentastarch or hydroxyethyl starch rather than a crystalloid solution [29-36]:

●Crystalloid versus albumin: In the Saline versus Albumin Fluid Evaluation (SAFE) trial, 6997 critically ill patients were randomly assigned to receive 4 percentalbumin solution or normal saline for up to 28 days [29]. There were no differences between groups for any endpoint, including the primary endpoint, mortality. Among the patients with severe sepsis (18 percent of the total group), there were also no differences in outcome. In another multicenter open-label randomized trial of patients with severe sepsis or septic shock, the addition of albumin to crystalloid did not improve survival compared to crystalloid alone (31 versus 32 percent) [30].

●Crystalloid versus hydroxyethyl starch: In the Scandinavian Starch for Severe Sepsis and Septic Shock (6S) trial, 804 patients with severe sepsis were randomly assigned to receive either 6 percent hydroxyethyl starch or Ringer’s acetate at a volume of up to 33 mL/kg of ideal body weight per day [31]. When assessed 90 days after randomization, mortality was increased in the hydroxyethyl starch group (51 versus 43 percent) and more patients in the hydroxyethyl starch group had required renal replacement therapy at some time during their illness (22 versus 16 percent).

●Crystalloid versus pentastarch The Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) trial compared pentastarch to modified Ringer's lactate in patients with severe sepsis and found no difference in 28-day mortality [32]. The trial was stopped early because there was a trend toward increased 90-day mortality among patients who received pentastarch.

In our clinical practice, we generally use a crystalloid solution instead of albumin solutionbecause of the lack of clear benefit and higher cost of albumin. We believe that giving a sufficient quantity of intravenous fluids rapidly and targeting appropriate goals is more important than the type of fluid chosen. We do not use hydroxyethyl starch or pentastarchthe Society of Critical Care Medicine guidelines [6]. (See"Treatment of severe hypovolemia or hypovolemic shock in adults", section on 'Choice of replacement fluid'.)  

Vasopressors — 

Vasopressors are second line agents in the treatment of sepsis and septic shock; we prefer intravenous fluids as long as they increase perfusion without seriously impairing gas exchange [37]. However, intravenous vasopressors are useful in patients who remain hypotensive despite adequate fluid resuscitation or who develop cardiogenic pulmonary edema.

In most patients with septic shock, we prefer to use norepinephrine (table 3) [4,6,38]. However, we find phenylephrine (a pure alpha-adrenergic agonist) to be useful when tachycardia or arrhythmias preclude the use of agents with beta-adrenergic activity (eg, norepinephrine). Choosing a vasopressor agent is discussed in greater detail elsewhere. (See "Use of vasopressors and inotropes", section on 'Choice of agent in septic shock'.)

Additional therapies — 

There is conflicting evidence on the use of additional therapies, such as inotropic therapy or red blood cell transfusion. Such therapies are targeted at increasing the cardiac output to improve tissue perfusion and thereby raise the central venous (superior vena cava) oxyhemoglobin saturation toward normal (ScvO2 ≥70 percent). We prefer that their use be limited to those with refractory shock in whom the ScvO2 remains <70 percent after optimization of intravenous fluid and vasopressor therapy.

Inotropic therapy — 

A trial of inotropic therapy may be warranted in patients who have refractory shock who also have diminished cardiac output [4,5,17,39,40]. Inotropic therapy should not be used to increase the cardiac index to supranormal levels [4]. Dobutamine is the usual inotropic agent [6]. At low doses, dobutamine may cause the blood pressure to decrease because its peripheral effects can dilate the systemic arteries. However, as the dose is increased, blood pressure usually rises because cardiac output increases out of proportion to the fall in peripheral vascular resistance. (See "Use of vasopressors and inotropes", section on 'Dobutamine'.)

Red blood cell transfusions — 

Based upon clinical experience, randomized studies, and guidelines on transfusion of blood products in critically ill patients, we typically reserve red blood cell transfusion for patients with a hemoglobin level ≤7 g per deciliter. Exceptions include suspicion of concurrent hemorrhagic shock or active myocardial ischemia.

Support for a restrictive transfusion strategy (goal hemoglobin >7 g/dL) is derived from direct and indirect evidence from randomized studies of patients with septic shock:

•One multicenter randomized study of 998 patients with septic shock reported no difference in 28 day mortality between patients who were transfused when the hemoglobin was ≤7 g/dL (restrictive strategy) and patients who were transfused when the hemoglobin was ≤9 g/dL (liberal strategy) [41]. The restrictive strategy resulted in 50 percent fewer red blood cell transfusions (1545 versus 3088 transfusions) and did not have any adverse effect on the rate of ischemic events (7 versus 8 percent).

•Data from randomized studies of EGDT that use red blood cell transfusion as part of the protocol for treating patients with sepsis are conflicting. While one trial initially reported a mortality benefit from EGDT that included transfusing patients to a goal hematocrit >30 (hemoglobin level 10 g/dL) [17], two similarly designed studies published since then reported no benefit to this strategy [18,19]. These studies are discussed below. (See 'Protocol-directed therapy'below.)

In further support of a restrictive approach to transfusion in patients with septic shock is the consensus among experts that transfusing to a goal of >7 g/dL is also preferred in critically ill patients without sepsis [42-44]. The use of blood transfusions in critically-ill patients is discussed in detail separately. (See "Use of blood products in the critically ill", section on 'Red blood cells'.)

Goals of initial resuscitation — 

The goal of fluid resuscitation is early restoration of perfusion to prevent or limit multiple organ dysfunction, as well as to reduce mortality.

The term "early goal-directed therapy" (EGDT) refers to the administration of intravenous fluids within the first six hours of presentationusing physiologic targets to guide fluid management. EGDT has gained widespread acceptance in clinical practice but the optimal targets are unknown.

Early goal-directed therapy targets — 

Although evidence is conflicting regarding the routine measurement of early goal-directed therapy targets, we suggest measuring the following targets for fluid management in patients with sepsis:

●Mean arterial pressure (MAP) ≥65 mmHg (MAP = [(2 x diastolic) + systolic]/3)(calculator 1)

●Urine output ≥0.5 mL/kg/hour

●Static or dynamic predictors of fluid responsiveness, eg, CVP 8 to 12 mmHg when central access is available (static measurement) or respiratory changes in the radial artery pulse pressure (dynamic measurement).

●Central venous (superior vena cava) oxyhemoglobin saturation (ScvO2) ≥70 percent (when central access is available) or mixed venous oxyhemoglobin saturation (SvO2) ≥65 percent (if a pulmonary artery catheter is being used).

Lactate clearance should be followed as a target in patients with sepsis to ensure a trend that demonstrates adequate clearance with therapy. Newer point of care analyzers are commercially available that may allow clinicians to follow lactate levels at the bedside more readily [45-47].  

The optimal physiologic target(s) of EGDT is unknown. There is also conflicting evidence on the value of measuring such targets, particularly CVP and ScVO2, which require central catheter placement [17-19,48]. In addition, the generalizability of a standard targeted approach to both resource-poor and resource-rich facilities is unknown. We prefer measuring MAP and urine output as universal targets that can be readily measured in all patients with sepsis, with the addition of CVPand/or ScVO2 in those in whom central access is otherwise required. This approach differs slightly from that of The Surviving Sepsis Campaign guidelines that recommend central venous access for CVP/ScvO2 measurement together with MAP and urine output in all patients with sepsis [6]. However, these guidelines were created before the results of three major randomized trials (ProCESS, ARISE, ProMISe), that showed no mortality benefit to an EGDT-based approach, were published [18,19,48,49].

Evidence that supports the use of EGDT targets is described below:

●CVP, MAP and urine output –

CVP 8 to 12 mmHg, MAP ≥65 mmHg (calculator 1), and urine output ≥0.5 mL/kg per hour are common EGDT targets used in clinical practice. Support for their use is derived from clinical experience and their use in the single randomized trial that studied them with and without ScvO2 [17]. They have not been compared to each other nor have they been proven to be superior to any other target or to clinical assessment.

The ideal targets for MAP, CVP, and urine output are unknown. One trial that randomized patients to a target MAP of 65 to 70 mmHg (low target MAP) or 80 to 85 mmHg (high target MAP) reported no mortality benefit to targeting a higher MAP [50,51]. Patients with a higher MAP had a greater incidence of atrial fibrillation (7 versus 3 percent), suggesting that targeting a MAP >80 mmHg is potentially harmful.

●ScvO2 –

Evidence from randomized trials that study the value of ScvO2) report mixed results. While one early trial of patients with septic shock reported a mortality benefit to targeting ScvO2 ≥70 percent in a protocol-based therapy, trials published since then (ProCESS, ARISE, ProMISe) have reported no mortality benefit [17-19,48'Protocol-directed therapy' below.)

●Lactate clearance –

Although the optimal frequency is unknown, we follow serum lactate (eg, every six hours), as an additional EGDT target in patients with sepsis until the lactate value has clearly fallen.

The lactate clearance is defined by the equation [(initial lactate - lactate >2 hourslater)/initial lactate] x 100. The lactate clearance and interval change in lactate over the first 12 hours of resuscitation has been evaluated as a potential marker for effective resuscitation [52,53]. One trial randomly assigned 300 patients with severe sepsis to undergo resuscitation targeting either a lactate clearance ≥10 percent or an ScvO2 ≥70 percent (other than these targets, the resuscitation protocols that included MAP, CVP, and urine output targets were identical) [52]. There was no difference in hospital mortality, length of stay, ventilator-free days, or incidence of multiorgan failure, suggesting that lactate clearance criteria may be an acceptable alternative to ScvO2criteria.

After the restoration of perfusion, lactate is a poor marker of tissue perfusion [54]. As a result, lactate values are generally unhelpful following restoration of perfusion, with one exception that a rising lactate level should prompt reevaluation of perfusion. (See "Venous blood gases and other alternatives to arterial blood gases".)

●Other –

Dynamic indices have been studied as a potential target to guide fluid management in sepsis. Respiratory changes in the vena caval diameter, radial artery pulse pressure, aortic blood flow peak velocity, and brachial artery blood flow velocity are considered dynamic hemodynamic measures, whereas CVP, MAP, ScvO2 and pulmonary artery occlusion pressure are considered static hemodynamic measures [55,56]. There is increasing evidence that dynamic measures are more accurate predictors of fluid responsiveness than static measures, as long as the patients are in sinus rhythm and passively ventilated with a sufficient tidal volume [20,57,58]. For actively breathing patients or those with irregular cardiac rhythms, an increase in the cardiac output in response to a passive leg-raising maneuver (measured by echocardiography, arterial pulse waveform analysis, or pulmonary artery catheterization) is a sensitive and specific predictor of fluid responsiveness [59]. Large randomized studies will be needed proving the efficacy of assessing dynamic measurement in response to intravenous fluids before they can be routinely applied to patients for the management of sepsis.

Protocol-directed therapy — Protocols targeted at the use of a combination of physiologic endpoints to guide fluid management in patients with sepsis and septic shock are common practice [17-19,48,49,60-62]. Typically, they combine the EGDT targets (ScvO2, CVP, MAP (calculator 1) and urine output, lactate) for fluid management with early administration of antibiotics, both within the first six hours of presentation.

There is conflicting evidence regarding the value of protocol-based therapy for sepsis [17-19,48,49,62-64]:

●One single center randomized trial of 263 patients with severe sepsis or septic shock compared a protocol that included targeting ScvO2 ≥70 percent, CVP 8 to 12 mmHg, MAP ≥65 mmHg, and urine output ≥0.5 mL/kg/hour to conventional therapy that targeted CVP, MAP, and urine output only [17]. Both groups initiated therapy (including antibiotics) within six hours of presentation. Mortality was lower in the group where all four targets were used (31 versus 47 percent), suggesting that targeting ScvO2, CVP, MAP, and urine output was a superior strategy. There was a heavy emphasis on the use of red cell transfusion (for a hematocrit >30) anddobutamine in order to reach the ScvO2target in this trial. In addition, the results of this trial may not be generalizable due to the inclusion of a significant number of sick patients with liver and heart disease that may have potentially biased the outcome favorably.

●A multicenter randomized trial (ProCESS) of 1341 patients with septic shock reported no mortality benefit with protocol-based therapies [18]. A protocol-based therapy that used all of the EGDT targets (ScvO2, CVP, MAP and urine output; protocol-based EGDT; central access required) was compared to a protocol that used some of the EGDT targets (MAP and urine output; protocol-based standard therapy; central access not required) and to usual care (no protocol used to direct fluid management). There were no differences in 60-day mortality between the groups (21 versus 18 versus 19 percent).

Two similarly designed multicenter randomized trials of 1600 (ARISE) and 2160 (ProMISe) patients with septic shock also reported no mortality benefit from EGDT [19,48]. In ARISE, compared to usual care, the 90 day mortality of 19 percent was similar in patients who received EGDT using the traditional targets outlined in prior studies [19]. Similarly, in ProMISe, the 90 day mortality was no different (29 percent) between the EGDT and usual care groups [48].

One explanation for the apparent negative results from these three trials may be that central line placement was common (>50 percent) in patients receiving protocol-based standard therapy and usual care; it is likely that CVP and ScvO2 were measured and targeted in these patients as well. Lack of benefit may also be attributed to overall better outcomes in these studies, perhaps due to early administration of antibiotics (70 to 100 percent before randomization) in all groups, and to improved clinical performance by highly trained clinicians in academic centers during an era that follows an aggressive sepsis education and management campaign.

Timing and duration — 

The early administration of fluid appears to be more important than volume or type of fluid in reducing mortality associated with sepsis. Based upon evidence from randomized studies and meta-analyses, we favor the initiation of fluid resuscitation within six hours of presentation. Once the targets of resuscitation are met and perfusion is restored, fluids can be reduced or stopped, and occasionally patients can be diuresed, when necessary. Resolution of sepsis and septic shock can take as little as a few hours or can be protracted to days or weeks.

A 2008 meta-analysis of randomized trials that initiated resuscitation targeting specific physiologic endpoints reported that compared to standard care, only trials that initiated resuscitation within 24 hours of the onset of sepsis showed a mortality benefit (39 versus 57 percent, odds ratio 0.50, 95% CI 0.37-0.69) [65]. In contrast, analysis of randomized trials that initiated therapy more than 24 hours after the onset of sepsis found no difference in mortality (64 versus 58 percent for standard resuscitation, odds ratio 1.16, 95% CI 0.60-2.22).

There are two possible outcomes following the interventions described above:

●Inadequate perfusion –

Despite aggressive therapy, the patient may have persistent hypoperfusion and progressive organ failure. This should prompt reassessment of the adequacy of the above therapies, antimicrobial regimen, and control of the septic focus, as well as the accuracy of the diagnosis and the possibility that unexpected complications or coexisting problems have intervened (eg, pneumothorax following CVC insertion).

●Adequate perfusion –

Patients who respond to therapy should have the rate of fluid administration reduced or stopped, and vasopressor support weaned. Patients should also continue to have their clinical and laboratory parameters followed closely. These include blood pressure, arterial lactate, urine output, creatinine, platelet count, Glasgow coma scale score, serum bilirubin, liver enzymes, oxygenation (ie, arterial oxygen tension or oxyhemoglobin saturation), and gut function (table 4). Reevaluation is indicated if any of these parameters worsen or fail to improve.  


Prompt identification and treatment of the primary site or sites of infection are essential [66-68]. This is the primary therapeutic intervention, with most other interventions being purely supportive. Antibiotics should be administered within the first six hours of presentation or earlier.

Identification of the septic focus — A careful history and physical examination may yield clues to the source of sepsis and help guide microbiologic evaluation (table 5). As an example, sepsis arising after trauma or surgery is often due to infection at the site of injury or surgery. The presence of a urinary or vascular catheter increases the chances that these are the source of sepsis.

Gram stain of material from sites of possible infection may give early clues to the etiology of infection while cultures are incubating. As examples, urine should be routinely analyzed via dipstick for leukocyte esterase, Gram stained, and cultured; sputum should be examined in a patient with a productive cough; and an intra-abdominal collection in a postoperative patient should be percutaneously sampled under ultrasound or other radiologic guidance.

Blood should be drawn from two distinct venipuncture sites and inoculated into standard blood culture media (aerobic and anaerobic). For patients with a vascular catheter, blood should be obtained both through the catheter and from another site [6]. (See "Blood cultures for the detection of bacteremia".)

If invasive candida or aspergillus infection is suspected, serologic assays for 1,3 beta-D-glucan, galactomannan, and anti-mannan antibodies, if available, may provide early evidence of these fungal infections [6]. The limitations of these assays and their role in the diagnosis of fungal infection are discussed separately. (See "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults", section on 'Non-culture methods' and "Diagnosis of invasive aspergillosis", section on 'Galactomannan antigen detection' and "Diagnosis of invasive aspergillosis", section on 'Beta-D-glucan assay'.)

There is no single test that immediately confirms the diagnosis of severe sepsis or septic shock. However, several laboratory tests, all of which are still investigational, have been studied as diagnostic markers of active bacterial infection [3]:

●Elevated serum procalcitonin levels are associated with bacterial infection and sepsis [69-71]. Despite this, a meta-analysis of 18 studies found that procalcitonin did not readily distinguish sepsis from nonseptic systemic inflammation (sensitivity of 71 percent and specificity of 71 percent) [70]. An additional randomized trial and another meta-analysis found that using clinical algorithms based upon procalcitonin levels did not affect mortality or duration of antibiotic treatment [72,73].

●The plasma concentration of soluble TREM-1 (triggering receptor expressed on myeloid cells), a member of the immunoglobulin superfamily that is specifically upregulated in the presence of bacterial products, is increased in patients with sepsis [74-76]. In a small trial, increased TREM-1 levels were both sensitive and specific for the diagnosis of bacterial sepsis (96 and 89 percent, respectively) [74]. However, a subsequent prospective cohort study found that increased TREM-1 levels predicted sepsis with a sensitivity and specificity of only 53 and 86 percent, respectively [77]. Serial monitoring of TREM-1 may also provide prognostic information in patients with established sepsis [75,76].

●Increased expression of CD64 on polymorphonuclear leukocytes indicates cellular activation and has been shown to occur in patients with sepsis [78,79]. In a prospective cohort study of 300 consecutive critically ill patients, increased CD64 expression predicted sepsis with a sensitivity of 84 percent and a specificity of 95 percent [77]. In this study, the sensitivity and specificity of increased CD64 expression were superior to that of increased procalcitonin or TREM-1 levels.

The combination of procalcitonin levels, TREM-1 levels, and CD64 expression appears to be superior to the use of any of these markers alone. However, evaluation of the clinical usefulness of such biomarkers is still in its early stages and should be considered preliminary. Until additional clinical investigations have been performed, we do not suggest the routine use of such biomarkers to identify sepsis.

Eradication of infection — Prompt and effective treatment of the active infection is essential to the successful treatment of sepsis and septic shock [6]. Source control (physical measures undertaken to eradicate a focus of infection and eliminate or treat ongoing microbial proliferation and infection) should be undertaken since undrained foci of infection may not respond to antibiotics alone (table 2). As examples, potentially infected foreign bodies (eg, vascular access devices) should be removed when possible, and abscesses should undergo percutaneous or surgical drainage. Some patients require extensive soft tissue debridement or amputation; in severe cases, fulminant Clostridium difficile-associated colitis may necessitate colectomy [80].

Antimicrobial regimen — 

Intravenous antibiotic therapy should be initiated within the first six hours or earlier (eg, within one hour), after obtaining appropriate cultures, since early initiation of antibiotic therapy is associated with lower mortality [4,81]. The choice of antibiotics can be complex and should consider the patient's history (eg, recent antibiotics received [82]), comorbidities, clinical context (eg, community- or hospital-acquired), Gram stain data, and local resistance patterns [4,83,84].

Poor outcomes are associated with inadequate or inappropriate antimicrobial therapy (ie, treatment with antibiotics to which the pathogen was later shown to be resistant in vitro) [85-91]. They are also associated with delays in initiating antimicrobial therapy, even short delays (eg, an hour).

●A prospective cohort study of 2124 patients demonstrated that inappropriate antibiotic selection was surprisingly common (32 percent) [88]. Mortality was markedly increased in these patients compared to those who had received appropriate antibiotics (34 versus 18 percent).

●A retrospective analysis of 2731 patients with septic shock demonstrated that the time to initiation of appropriate antimicrobial therapy was the strongest predictor of mortality [89].

When the potential pathogen or infection source is not immediately obvious, we favor broad-spectrum antibiotic coverage directed against both gram-positive and gram-negative bacteria. Few guidelines exist for the initial selection of empiric antibiotics in severe sepsis or septic shock.

Staphylococcus aureus is associated with significant morbidity if not treated early in the course of infection [92]. There is growing recognition that methicillin-resistant S. aureus (MRSA) is a cause of sepsis not only in hospitalized patients, but also in community dwelling individuals without recent hospitalization [93,94]. For these reasons, we recommend that severely ill patients presenting with sepsis of unclear etiology be treated with intravenous vancomycin (adjusted for renal function) until the possibility of MRSA sepsis has been excluded. Potential alternative agents to vancomycin (eg, daptomycin for non-pulmonary MRSA, linezolid, ceftaroline) should be considered for patients with refractory or virulent MRSA, or a contraindication to vancomycin. These agents are discussed separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia and osteomyelitis", section on 'Bacteremia' and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Methicillin-resistant Staphylococcus aureus'.)

In our practice, if Pseudomonas is an unlikely pathogen, we favor combining vancomycin with one of the following:

●Cephalosporin, 3rd generation (eg,ceftriaxone or cefotaxime) or 4th generation (cefepime), or

●Beta-lactam/beta-lactamase inhibitor (eg,piperacillin-tazobactam, ticarcillin-clavulanate), or

●Carbapenem (eg, imipenem or meropenem)

Alternatively, if Pseudomonas is a possible pathogen, we favor combining vancomycin with two of the following (see "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections"):

●Antipseudomonal cephalosporin (eg,ceftazidime, cefepime), or

●Antipseudomonal carbapenem (eg,imipenem, meropenem), or

●Antipseudomonal beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillin-clavulanate), or

●Fluoroquinolone with good anti-pseudomonal activity (eg, ciprofloxacin), or

●Aminoglycoside (eg, gentamicin, amikacin), or

●Monobactam (eg, aztreonam)

Selection of two agents from the same class, for example, two beta-lactams, should be avoided. We emphasize the importance of considering local susceptibility patterns when choosing an empiric antibiotic regimen.

After culture results and antimicrobial susceptibility data return, we recommend that therapy be pathogen- and susceptibility-directed, even if there has been clinical improvement while on the initial antimicrobial regimen. Gram-negative pathogens have historically been covered with two agents from different antibiotic classes. However, several clinical trials and two meta-analyses have failed to demonstrate superior overall efficacy of combination therapy compared to monotherapy with a third generation cephalosporin or a carbapenem [88,95-99]. Furthermore, one meta-analysis found double coverage that included an aminoglycoside was associated with an increased incidence of adverse events (nephrotoxicity) [98,99]. For this reason, in patients with gram negative pathogens, we recommend use of a single agent with proven efficacy and the least possible toxicity, except in patients who are either neutropenic or whose sepsis is due to a known or suspected Pseudomonas infection [4,97]. (See "Pseudomonas aeruginosa bacteremia and endocarditis" and "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections".)

Regardless of the antibiotic regimen selected, patients should be observed closely for toxicity, evidence of response, and the development of nosocomial superinfection [100]. There are no published randomized controlled trials testing safety of de-escalation of antibiotic therapy in adult patients with sepsis or septic shock [101]. The duration of therapy is typically 7 to 10 days, although longer courses may be appropriate in patients who have a slow clinical response, an undrainable focus of infection, or immunologic deficiencies [4]. In patients who are neutropenic, antibiotic treatment should continue until the neutropenia has resolved or the planned antibiotic course is complete, whichever is longer. In non-neutropenic patients in whom infection is thoroughly excluded, antibiotics should be discontinued to minimize colonization or infection with drug-resistant microorganisms and superinfection with other pathogens.

Other agents — Invasive fungal infections occasionally complicate the course of critical illness in non-neutropenic patients, especially when the following risk factors are present: surgery, parenteral nutrition, prolonged antimicrobial treatment, septic shock or multisite colonization with Candida spp. To limit the risk of candida-related mortality empirical anti-fungal treatments have been proposed. In a meta-analysis of 22 studies (most often comparing fluconazole to placebo, but also using ketoconazole, anidulafungin,caspofungin, micafungin, and amphotericin B), untargeted empiric antifungal therapy possibly reduced fungal colonization and the risk of invasive fungal infection but did not reduce all-cause mortality [102]. Similarly, in a study of critically-ill patients ventilated at least five days, empiric antifungal treatment (mostly fluconazole) was not associated with a decreased risk of mortality or occurrence of invasive candidiasis [103]. Thus, the routine administration of empirical antifungal therapy is not warranted in non-neutropenic critically-ill patients.


Glucocorticoids — 

Glucocorticoids have long been investigated as therapeutic agents in sepsis because the pathogenesis of sepsis involves an intense and potentially deleterious host inflammatory response. Evidence from randomized trials suggest that corticosteroid therapy is most likely to be beneficial in patients who have severe septic shock (defined as a systolic blood pressure <90 mmHg) that is unresponsive to adequate fluid resuscitation and vasopressor administration. Data from ongoing clinical trials are needed to confirm that benefit. This topic is discussed in detail separately. (See "Corticosteroid therapy in septic shock".)

Nutrition — 

There is consensus that nutritional support improves nutritional outcomes in critically ill patients, such as body weight and mid-arm muscle mass. However, it is uncertain whether nutritional support improves important clinical outcomes (eg, duration of mechanical ventilation, length of stay, mortality), or whether there is a validated role for specific supplements (eg, immune modulators). The principles of nutritional support in patients with sepsis should parallel that in critically ill patients, which is reviewed in detail elsewhere. (See "Nutrition support in critically ill patients: An overview".)

Venous thromboembolism prophylaxis — 

Patients with sepsis and septic shock are at increased risk for venous thromboembolism such that patients should receive thromboprophylaxis [104], the details of which are discussed separately. (See"Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".)

Intensive insulin therapy — 

Hyperglycemia and insulin resistance are common in critically ill patients, independent of a history of diabetes mellitus [105]. The optimal blood glucose range is controversial. Most clinicians target blood glucose levels between 140 and 180 mg/dL (7.7 to 10 mmol/L). This topic is discussed separately. (See "Glycemic control and intensive insulin therapy in critical illness".)

External cooling or antipyretics — 

Controlling fever during sepsis and septic shock has potential benefits and adverse effects, the net effects of which are uncertain.

A trial was performed to compare the effects of external cooling with no external cooling. External cooling consists of using either an automatic cooling blanket, or ice-cold bed sheets and ice packs, to achieve a core body temperature of 36.5 to 37°C for 48 hours. It decreases the time to fever control without exposing the patient to potential adverse effects of antipyretic drugs. The trial randomly assigned 200 patients with septic shock (the patients were requiring vasopressors, mechanically ventilated, and sedated) to receive either external cooling or no external cooling [106]. Patients in the external cooling group had lower 14-day mortality (19 versus 34 percent) and were more likely to have their vasopressor dose lowered by 50 percent (54 versus 20 percent) and their shock reversed during their ICU stay (86 versus 73 percent). No antipyretic agents were received during the trial.

While these results are promising, we believe that the results need to be confirmed before external cooling is adopted as routine clinical practice. Among the limits of the trial, patients in the external cooling group may have been less severely ill (ie, they required a lower baseline vasopressor dose), the trial was not blinded so co-interventions cannot be excluded, and there were relatively few events (ie, deaths, patients with a 50 percent vasopressor dose decrease, and patients with shock reversal), which lowers confidence in the accuracy of the estimated effects. Moreover, the results suggest that external cooling is preferable to no cooling, but they do not provide guidance about whether external cooling is preferable to antipyretic medications.

The role of antipyretics for fever control in critically ill patients is also of uncertain benefit and is discussed separately. (See "Fever in the intensive care unit", section on 'Management'.)

Investigational therapies — 

A variety of investigational therapies including cytokine and toxin inactivation, as well as hemofiltration, statins, and beta blockade are discussed in detail separately. (See "Investigational and ineffective therapies for sepsis".)


UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topic (see "Patient education: Sepsis in adults (The Basics)")


●Therapeutic priorities for patients with sepsis and septic shock include securing the airway, correcting hypoxemia, and administering fluids and antibiotics. Intubation and mechanical ventilation are required in some patients. (See'Therapeutic priorities' above and 'Stabilize respiration' above.)

●The adequacy of perfusion should be assessed in patients with suspected sepsis and septic shock. Hypotension is the most common indicator of inadequate perfusion. However, critical hypoperfusion can also occur in the absence of hypotension, especially during early sepsis. Common signs of hypoperfusion include warm, vasodilated skin in early sepsis that progresses to cool, vasoconstricted skin in late sepsis, tachycardia >90 per min, obtundation or restlessness, oliguria or anuria, and lactic acidosis. (See 'Assess perfusion' above.)

●For patients with sepsis and septic shock, we recommend intravenous fluids, rather than vasopressors, inotropes, or red blood cell transfusions as first-line therapy for the restoration of tissue perfusion (Grade 1B). Therapy should be initiated as early as possible, within six hours of presentation. Fluid boluses are the preferred method of administration and should be repeated until blood pressure and tissue perfusion are acceptable, pulmonary edema ensues, or there is no further response. These parameters should be assessed before and after each fluid bolus (See 'Interventions to restore perfusion' above.)

•For initial fluid replacement, we suggest using a crystalloid solution rather than albumin-containing solution (Grade 2B) and recommend that a hyperoncotic starch solution NOT be administered (Grade 1A'Choice of fluid' above and "Treatment of severe hypovolemia or hypovolemic shock in adults", section on 'Choice of replacement fluid'.)

•For patients who remain hypotensive following intravascular volume repletion, we recommend vasopressors (Grade 1B); the preferred initial agent is norepinephrine'Vasopressors' above and "Use of vasopressors and inotropes", section on 'Choice of agent in septic shock'.)

•For patients with sepsis and septic shock that are refractory to intravenous fluid and vasopressor therapy, additional therapies, such as inotropic therapy and blood transfusions, are administered based on individual assessment. We typically reserve red blood cell transfusion for patients with a hemoglobin level <7 g per deciliter. (See 'Additional therapies' above and "Use of vasopressors and inotropes", section on 'Choice of agent in septic shock'.)

●For most patients with sepsis and septic shock, we suggest fluid management be guided using specific targets (early goal-directed therapy [EGDT]), rather than being managed without specific therapeutic targets. The optimal target to guide fluid management is unknown. For most patients, we target mean arterial pressure ≥65 mmHg (calculator 1) and urine output ≥0.5 mL/kg/hour and integrate it with static measures of determining adequacy of fluid administration (eg, central venous pressure [CVP] 8 to 12 mmHg), or dynamic predictors of fluid responsiveness (eg, respiratory changes in the radial artery pulse pressure) or central venous oxygen saturation ≥70 percent. In addition, we follow serum lactate (eg, every six hours), until there is a clear clinical response. (See'Goals of initial resuscitation' above.)

●Prompt identification and treatment of the site of infection are essential. Sputum and urine should be collected for Gram stain and culture. Intra-abdominal fluid collections should be percutaneously sampled. Blood should be taken from two distinct venipuncture sites and from indwelling vascular access devices and cultured aerobically and anaerobically. (See 'Identification of the septic focus'above.)

●Antibiotics should be administered within six hours of presentation, preferably after appropriate cultures have been obtained. We recommend empiric broad spectrum antibiotics when a definite source of infection cannot be identified (Grade 1B). The routine administration of antifungal therapy is not warranted in non-neutropenic patients. (See 'Antimicrobial regimen' above.)

●Potentially infected vascular access devices should be removed (if possible), abscesses should be drained, and extensive soft tissue infections should be debrided or amputated (table 2'Eradication of infection' above.)

●Glucocorticoid therapy, nutritional support, glucose control, and investigational therapies are additional considerations in the management of patients with severe sepsis or septic shock. Each is discussed separately. (See "Corticosteroid therapy in septic shock" and "Nutrition support in critically ill patients: An overview" and"Glycemic control and intensive insulin therapy in critical illness" and"Investigational and ineffective therapies for sepsis".)


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Evaluation and Treatment for Sepsis
-Dr M A Aleem


Approach and Considerations

Early aggressive medical therapy is indicated in patients with suspected sepsis, based on the organ source of sepsisHowever, it is crucial to consider pseudosepsis as a cause of the presenting syndrome complex because most causes of pseudosepsis are readily treatable and reversible if recognized and treated early. Patients with pseudosepsis require supportive therapy rather than antimicrobial treatment.

Patients with sepsis are generally ill and require bed rest or admission to the intensive care unit (ICU) for monitoring and treatment. Admission to an ICU or surgical ICU depends on the severity of the septic process and the degree of organ dysfunction, as well as the need for surgical intervention. Transfer to a facility able to perform diagnostic imaging tests or required surgical procedures if they are not available at the admitting hospital may be necessary.

Determine the likely source of the infection, and administer intravenous (IV) empiric antimicrobial agents until culture results become available, at which point more narrow-spectrum agents can be used (see below). In addition, offer supportive therapy aimed at maintaining organ perfusion, and provide respiratory support when necessary.

In a prospective study of 5787 adults with severe sepsis or septic shock, reported at the 2013 Scientific Assembly of the American College of Emergency Physicians, patients triaged and managed according to 4 clinical goals (blood cultures before antibiotics, lactate before 90 minutes, IV antibiotics before 180 minutes, and 30 mL/kg of IV fluids before 180 minutes) were significantly less likely to die in the hospital than were those for whom all 4 of these goals were not met (22.6% vs 26.5%, respectively).

In a multivariate regression analysis adjusted for age, admission to the intensive care unit (ICU), vasopressor initiation, central venous catheter insertion, and monitoring of central venous pressure and central venous oxygen saturation, complete compliance with the clinical goals was associated with a survival odds ratio of 1.194 (1.04-1.37).

Surgical Intervention

Early evaluation by a surgeon for patients with presumed intra-abdominal or pelvic sepsis is essential, because surgical intervention may be required for cure or resolution of the infection. For example, peritonitis may result in abscesses, which may subsequently need to be drained. Inadequate correction of intra-abdominal perforation or drainage procedures may result in a continuance or relapse of the patient’s septic condition.

The procedures used are dependent on the source of the infection, the severity of the sepsis, the patient’s clinical status, among other factors in individual scenarios.

Coordinate surgical follow-up with the surgeon.


Obtain a consultation with a surgeon for patients with presumed intra-abdominal or pelvic sepsis. Early surgical consultation and involvement by the surgical team is essential, because many causes of sepsis involve a perforated viscus, abscess, or obstructing process that requires surgical intervention for cure or resolution of the infection.

Also obtain a consultation with an infectious disease specialist for all patients with sepsis included in the differential diagnosis.

Antimicrobial Therapy

Appropriate antimicrobial therapy depends on adequate coverage of the resident flora of the organ system presumed to be the source of the septic process.Agents suitable for empiric monotherapy regimens (depending on the source and underlying microbiology of the sepsis because the agent must be able to cover all of the likely pathogens) may include the following:







Combination therapeutic regimens include metronidazole plus either levofloxacin, aztreonam, or an aminoglycoside. Many advocate using antistaphylococcal coverage (eg, vancomycin) with an extended cephalosporin, beta-lactam/beta-lactamase inhibitor antibiotic, or a carbapenem.

Although no drug regimen may be superior to another, time to first dose administration is very important. Mortality data suggest that early administration of appropriate antibiotics is correlated with better survival. Alternative agents may be used alone or in combination, with a good adverse-effect profile.

Antibiotics are normally continued until the septic process and surgical interventions have controlled the source of infection. Ordinarily, patients are treated for approximately 2 weeks. As soon as patients are able to tolerate medications orally, they may be switched to an equivalent oral antibiotic regimen in an IV-to-oral conversion program.

Empiric therapy for IV line infections

Because IV line infections are most often due to Staphylococcus aureus [MRSA]) and less commonly due to aerobic gram-negative bacilli, the preferred empiric therapy for these infections is meropenem or cefepime plus additional coverage for staphylococci. If MRSA is prevalent in the institution, add linezolid, vancomycin, or daptomycin.

If coagulase-negative, methicillin-sensitive staphylococci are recovered from the blood (high-level bacteremia; that is, 3 or 4 positive blood cultures out of 4), avoid vancomycin for empiric therapy if possible; these are low-virulence organisms.

Treatment of staphylococcal central line infection may require removal of the line. If the central line cannot be removed for clinical reasons in a patient with MRSA or coagulase-negative staphylococcal infection, empiric suppressive vancomycin therapy is acceptable.

Minimize the use of vancomycin in order to prevent the emergence ofEnterococcus faecium, a vancomycin-resistant enterococci (VRE).

Empiric therapy for biliary tract infections

The main biliary tract pathogens includeEscherichia coli, Klebsiella species, andEnterococcus faecalis. Coverage for staphylococci is not needed in the biliary tract. Anaerobes are important only in patients with diabetes who haveClostridium perfringens emphysematous cholecystitis.

Preferred monotherapy regimens for biliary tract infections include imipenem, meropenem, ampicillin-sulbactam, or piperacillin-tazobactam.

Empiric therapy for intra-abdominal and pelvic infections

The main pathogens in the lower abdomen and pelvis include aerobic coliform gram-negative bacilli and B fragilis. Enterococci do not require special coverage. Potent anti– B fragilis and aerobic gram-negative bacillary coverage are essential, in addition to surgical intervention when drainage or repair of intra-abdominal viscera is required.

Preferred monotherapy regimens for intra-abdominal and pelvic infections include imipenem, meropenem, piperacillin-tazobactam, ampicillin-sulbactam, or tigecycline. Alternate combination therapy for intra-abdominal and pelvic infections consists of clindamycin or metronidazole plus aztreonam, levofloxacin, or an aminoglycoside. Some authors raise concerns about use of tigecycline.

Empiric therapy for urosepsis

The primary uropathogens include gram-negative aerobic bacilli, such as coliforms or enterococci (E faecalisPseudomonas aeruginosa, Enterobacterspecies, and Serratia species are rare uropathogens and are associated with urologic instrumentation.

Preferred monotherapy for urosepsis due to aerobic gram-negative bacilli employs aztreonam, levofloxacin, a third- or fourth-generation cephalosporin, or an aminoglycoside. However, preferred monotherapy for urosepsis due to enterococci (E faecalis) involves the use of ampicillin or vancomycin (penicillin-allergic). For VRE urosepsis, linezolid or daptomycin may be used.

Empiric therapy for community-acquired urosepsis consists of levofloxacin, aztreonam, or an aminoglycoside plus ampicillin. For nosocomial urosepsis, piperacillin-tazobactam, imipenem, or meropenem monotherapy is preferred.

Empiric therapy for staphylococcal, pneumococcal, and meningococcal sepsis

S aureus sepsis is usually associated with infection caused by devices or acute bacterial endocarditis. Empiric therapy may be with nafcillin, an antistaphylococcal agent, a cephalosporin, a carbapenem, daptomycin, or linezolid.

Pneumococcal or meningococcal sepsis may be treated with penicillin G or a beta-lactam. In patients with associated meningococcal meningitis, the antibiotic selected should penetrate the cerebrospinal fluid (CSF) and should be given in meningeal doses. Consider the regional prevalence of drug-resistant pneumococci when selecting an antibiotic.

Empiric therapy for sepsis of unknown origin

The usual sources of sepsis are the distal gastrointestinal (GI) tract, the pelvis, and the genitourinary (GU) tract. Organisms that should be covered from these areas include aerobic gram-negative bacilli (coliforms) and B fragilis. Enterococci are important pathogens in biliary tract sepsis and urosepsis.

Preferred empiric monotherapy includes meropenem, imipenem, piperacillin-tazobactam, or tigecycline.

Empiric combination therapy includes metronidazole plus either levofloxacin, aztreonam, cefepime, or ceftriaxone.

Outpatient management

If orally administered antibiotics are continued at home, advise the patient about possible adverse effects. If additional antimicrobial therapy is needed outside the hospital setting, it should be given orally, not intravenously. Do not allow the total course of antibiotics to exceed 3 weeks, except for the treatment of liver abscesses, which may require prolonged courses of oral antibiotics for cure or complete clinical resolution. 


Medication Summary

The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

Antibiotics, Other

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.


Imipenem-cilastatin is a carbapenem with activity against most gram-positive organisms (except MRSA), gram-negative organisms, and anaerobes. It is used for treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated owing to their potential for toxicity.


Meropenem is a carbapenem with slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared with imipenem. It is less likely to cause seizures and has superior penetration of the blood-brain barrier compared with imipenem.

Piperacillin and tazobactam

Piperacillin-tazobactam inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication. It has antipseudomonal activity.

Ampicillin and sulbactam

Ampicillin and sulbactam is a drug combination of a beta-lactamase inhibitor with ampicillin. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. It is an alternative to amoxicillin if the patient is unable to take medications orally. It covers skin, enteric flora, and anaerobes and is not ideal for nosocomial pathogens.


Clindamycin is primarily used for its activity against anaerobes. It has some activity against Streptococcus species and methicillin-sensitive S aureus (MSSA).


Metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. It is usually combined with other antimicrobial agents, except when used for Clostridium difficile enterocolitis, in which monotherapy is appropriate.


Cefepime is a fourth-generation cephalosporin. It has gram-negative coverage comparable to ceftazidime but has better gram-positive coverage (comparable to ceftriaxone). Cefepime is active against Pseudomonas species. It has increased effectiveness against extended-spectrum beta-lactamase (ESBL)–producing organisms. Its poor capacity to cross blood-brain barrier precludes its use for treatment of meningitis.


Levofloxacin is a fluoroquinolone with excellent gram-positive and gram-negative coverage. It is an excellent agent for pneumonia and has excellent abdominal coverage as well. High urine concentration necessitates reduced dosing in urinary tract infection.


Vancomycin provides gram-positive coverage and good hospital-acquired MRSA coverage. It is now used more frequently because of the high incidence of MRSA. Vancomycin should be given to all septic patients with indwelling catheters or devices. It is advisable for skin and soft-tissue infections.


The broad spectrum and action of trimethoprim and sulfamethoxazole (TMP-SMZ) against organisms found in patients with cystic fibrosis and the convenience of oral administration make this combination useful for treatment of milder infections in an outpatient setting.


Aztreonam is a monobactam, not a beta-lactam, antibiotic that inhibits cell wall synthesis during bacterial growth. It is active against gram-negative bacilli but has very limited gram-positive activity and is not useful for anaerobes. Aztreonam lacks cross-sensitivity with beta-lactam antibiotics. It may be used in patients who are allergic to penicillins or cephalosporins.

The duration of therapy depends on the severity of infection and is continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. Doses that are smaller than indicated should not be used.

Transient or persistent renal insufficiency may prolong serum levels. After the initial loading dose of 1 or 2 g, reduce the dose by one half for an estimated CrCl of 10-30 mL/min/1.73 m2. When only the serum creatinine concentration is available, the following formula (based on sex, weight, and age) can approximate CrCl (serum creatinine should represent a steady state of renal function):

• Males: CrCl = [(weight in kg)(140 - age)] divided by (72 X serum creatinine in mg/dL)

• Females: 0.85 X above value

In patients with severe renal failure (CrCl < 10 mL/min/1.73 m2), those supported by hemodialysis, a usual dose of 500 mg, 1 g, or 2 g is given initially.

The maintenance dose is one fourth of the usual initial dose given at the usual fixed interval of 6, 8, or 12 hours. For serious or life-threatening infections, supplement maintenance doses with one eighth of the initial dose after each hemodialysis session.

Elderly persons may have diminished renal function. Renal status is a major determinant of dosage in these patients. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by the kidneys, obtain estimates of CrCl and make appropriate dosage modifications. Insufficient data are available regarding intramuscular (IM) administration to pediatric patients or dosing in pediatric patients with renal impairment. Aztreonam is administered intravenously only to pediatric patients with normal renal function.


Linezolid is used as an alternative drug in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci. It is also effective against MRSA and penicillin-susceptible S pneumoniae infections.

This agent is an oxazolidinone antibiotic that prevents formation of the functional 70S initiation complex, which is essential for the bacterial translation process. Linezolid is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftriaxone is used for increasing prevalence of penicillinase-producing microorganisms. It inhibits bacterial cell wall synthesis by binding to 1 or more penicillin-binding proteins. Cell wall autolytic enzymes lyse bacteria, while cell wall assembly is arrested.


Daptomycin causes membrane depolarization by binding to components of the cell membrane of susceptible organisms. It inhibits DNA, RNA, and protein synthesis intracellularly. It is a bactericidal antibiotic.


Nafcillin is a broad-spectrum penicillin. It is used for methicillin-sensitive S aureus and is the initial therapy for suspected penicillin G–resistant streptococcal or staphylococcal infections. In severe infections, start with parenteral therapy and change to oral therapy as the condition warrants. Because of thrombophlebitis, particularly in elderly persons, administer parenterally for only 1-2 days; change to oral therapy as indicated clinically.

Rifampin (Rifadin)

Rifampin is for use in combination with at least 1 other antituberculosis drug. It inhibits RNA synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription. Cross-resistance may occur.


This is the first of a new antibiotic class called cyclic lipopeptides. It binds to bacterial membranes and causes rapid membrane potential depolarization, thereby inhibiting protein, DNA, and RNA synthesis, and ultimately causing cell death. It is indicated for complicated skin and skin structure infections caused by S aureus (including methicillin-resistant strains), S pyogenes, S agalactiae, S dysgalactiae, and E faecalis(vancomycin-susceptible strains only).


Tigecycline is a glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. It inhibits bacterial protein translation by binding to the 30S ribosomal subunit, and it blocks the entry of amino-acyl tRNA molecules in ribosome A site. It is indicated for complicated skin and skin structure infections caused by E coli, E faecalis(vancomycin-susceptible isolates only), S aureus (methicillin-susceptible and -resistant isolates), S agalactiae, S anginosus group (includes S anginosus, S intermedius, and S constellatus), S pyogenes and B fragilis.