Pharmacokinetic and Pharmacodynamic Considerations When Treating Patients with Sepsis and Septic Shock

  title={Pharmacokinetic and Pharmacodynamic Considerations When Treating Patients with Sepsis and Septic Shock},
  author={Peter de Paepe and Frans M. Belpaire and Walter Buylaert},
  journal={Clinical Pharmacokinetics},
Sepsis and septic shock are accompanied by profound changes in the organism that may alter both the pharmacokinetics and the pharmacodynamics of drugs. This review elaborates on the mechanisms by which sepsis-induced pathophysiological changes may influence pharmacological processes.Drug absorption following intramuscular, subcutaneous, transdermal and oral administration may be reduced due to a decreased perfusion of muscles, skin and splanchnic organs. Compromised tissue perfusion may also… 

Introduction to drug pharmacokinetics in the critically ill patient.

General principles of PK, including absorption, distribution, metabolism, and elimination, and how critical illness can influence these parameters are reviewed, to provide general suggestions for clinicians on how to modify drug regimens to manage PK challenges.

Impact of Severe Sepsis or Septic Shock on Drug Response

The dynamic status of sepsis in critically ill patients results in alterations in pharmacokinetic parameters so it is of importance drug concentration assessment in this population, different from healthy volunteers or less severe ill patients.

The impact of sepsis on hepatic drug metabolism in critically ill patients: a narrative review

Evidence is examined on whether hepatic drug metabolism is significantly affected in septic patients, and to provide insights in the need for future research on the pharmacokinetic behavior of hepatic metabolized drugs in sepsis.

Development of a Physiologically Based Pharmacokinetic Modelling Approach to Predict the Pharmacokinetics of Vancomycin in Critically Ill Septic Patients

PBPK modelling incorporating literature data and individual patient data is able to correctly predict vancomycin pharmacokinetics in septic patients and provides essential key parameters for further development of PBPK models and dose optimisation strategies in critically ill patients with sepsis.

Effects of Low-Dose Escherichia coli Lipopolysaccharide-Induced Endotoxemia on Morphine Pharmacokinetics in an Animal Model.

Low-dose endotoxemia is correlated with significant alterations in morphine pharmacokinetics in rabbits, leading to the faster elimination of the drug, implying the need to modify morphine dosing regimens to ensure optimal analgesia.

Towards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomes

Increase in both the dose and frequency of drug administration are warranted, at least in the early phase of treatment, because sepsis-induced metabolic acidosis promotes protonation, which increases renal clearance of basic drugs such as isoniazid and ethambutol, and hence AUCs are substantially reduced.

Regulation of drug metabolism and disposition during inflammation and infection

  • K. Renton
  • Biology, Medicine
    Expert opinion on drug metabolism & toxicology
  • 2005
For any drug that is metabolised by CYP and has a narrow therapeutic index, there is a significant risk in placing patients in a position where an infection or inflammatory response might lead to aberrant drug handling and an adverse drug response.

Continuous infusion of physostigmine in patients with perioperative septic shock: A pharmacokinetic/pharmacodynamic study with population pharmacokinetic modeling.




Effects of Surgery on the Pharmacokinetic Parameters of Drugs

Despite the lack of research into pharmacokinetics during the postoperative period, and given the immense and often sudden changes observed in patients post-surgery, it is reasonable to recommend vigilance with respect to drug therapy during this period.

Pharmacokinetic and Pharmacodynamic Considerations in Drug Therapy of Cardiac Emergencies

In the drug therapy of cardiac emergencies, it is necessary to rapidly achieve therapeutic drug concentrations and adjust drug dose as the patient’s clinical status changes, and drug pharmacokinetic and pharmacodynamic considerations to drug dosing in cardiac emergencies are illustrated.

Pharmacokinetics of Drugs Used in Critically Ill Adults

Understanding the underlying pathophysiology in the critically ill and applying pharmacokinetic principles in selection of drug and dose regimen is crucial to optimising the pharmacodynamic response and outcome.

Interrelationship Between Renal Haemodynamics, Drug Kinetics and Drug Action

The altered state of renal haemodynamics in turn may modify the pharmacological and pharmacokinetic properties of other drugs present in the body and this should be considered in determining the dose and frequency of drug administration.

Pharmacotherapy in shock syndromes: the neglected field of pharmacokinetics and pharmacodynamics.

The inclusion of therapeutic drug monitoring in clinical shock studies should be applied more frequently to establish experimental results in the "real world" of ICU settings.

Effect of hepatic insufficiency on pharmacokinetics and drug dosing

D dosage reduction is necessary for many drugs administered to patients with chronic liver disease such as liver cirrhosis, because of reduced liver blood flow and the systemic clearance of flow limited drugs and portal‐systemic shunting.

Physiologic Implications of Mechanical Ventilation on Pharmacokinetics

The physiologic effects of mechanical ventilation are reviewed and theoretical changes in the pharmacokinetics of concomitantly administered drugs are proposed to give clinicians guidelines for drug dosing in patients receiving mechanical ventilation.

Effect of altered volume of distribution on aminoglycoside levels in patients in surgical intensive care.

The apparent volume of distribution (Vd) of aminoglycosides was found to be increased in 100 patients in a surgical intensive care unit who had gram-negative pneumonia or intraabdominal sepsis and

High‐dose naloxone: Pharmacokinetics in patients in septic shock

In these critically ill patients there was virtually no drug elimination as levels were followed for 5 h post-termination of a 6-h infusion of 2.4 mg/kgh, explaining why responses have been reported by others to small doses of naloxone in septic shock patients.

Blood Flow and Adrenergic Drugs in Septic Shock

Restoration of circulating blood volume by fluid resuscitation reveals a hyperdynamic circulation with reduced systemic vascular resistance and normal or high cardiac output in septic shock.