Current Management of Gram-Negative Septic Shock

Jean-Louis Vincent; Wasineenart Mongkolpun


Curr Opin Infect Dis. 2018;31(6):600-605. 

In This Article

Abstract and Introduction


Purpose of review: Sepsis is a common condition in critically ill patients and associated with high morbidity and mortality. Sepsis is the result of infection by many potential pathogens, including Gram-negative bacteria. There are no specific antisepsis therapies and management relies largely on infection control and organ support, including hemodynamic stabilization. We discuss these key aspects and briefly mention potential immunomodulatory strategies.

Recent findings: New aspects of sepsis management include the realization that early treatment is important and that fluids and vasopressor agents should be administered simultaneously to insure rapid restoration of an adequate perfusion pressure to limit development and worsening of organ dysfunction. New immunomodulatory therapies, both suppressive and stimulatory, are being tested.

Summary: Early diagnosis enabling rapid treatment can optimize outcomes. The multiple components of adequate sepsis management necessitate a team approach.


Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[1] Patients with persisting hypotension requiring vasopressors to maintain mean arterial pressure more than 65 mmHg and a serum lactate level more than 2 mmol/l (18 mg/dl) despite adequate volume resuscitation are said to have septic shock.[1] Sepsis is largely caused by bacteria, but can also be the result of infection with other microorganisms including fungi, viruses, and parasites. Among the bacterial causes, Gram-negative and Gram-positive bacteria occur with similar frequency overall.[2] The most frequently isolated Gram-negative organisms in patients with sepsis are Escherichia coli, Klebsiella spp., Enterobacter, and Pseudomonas spp.[2]

The treatment of septic shock occurring as a result of Gram-negative organisms is currently not very different from the treatment of septic shock because of other organisms. There are some differences in initial microorganism recognition and signaling by pathogen-recognition receptors according to bacterial species and the precise patterns of mediator release and activation may vary depending on the invading pathogen.[3] However, there is considerable crosstalk and receptor collaboration[4,5] and these pathways ultimately converge leading to the same effects on cellular and organ function.[6,7] In the past, attempts were made to separate the hemodynamic presentation of sepsis ('warm' or 'cold' shock states) according to the type of microorganism,[8] but with improved understanding of the similar pathophysiological events regardless of causative microorganism, this approach has now been abandoned. Several studies have shown no differences in mortality rates according to bacterial class.[9] Indeed, outcomes are influenced by multiple other factors including appropriateness of initial antibiotics, antimicrobial sensitivity and virulence, source of infection, severity of illness, and patient age and comorbidities.[10–12]

The management of septic shock includes three major components, as shown in Figure 1. Importantly, infection control and hemodynamic support need to be performed promptly and together. In a classical experimental study in a model of peritonitis, Natanson et al.[13] showed that no animals survived with no treatment, 13% survived when treated with antibiotics or with cardiovascular stabilization, and when antibiotics and cardiovascular stabilization were combined, survival reached 43%.

Figure 1.

The three components of sepsis management.