‘Contaminated IV fluid kills 12 pregnant women’, ‘Indore pharma company raided after deaths of 12 women in Rajasthan’, ‘IV fluids worth Rs. 70 lakh frozen’, ‘IV fluids recalled from five States’ are few of the news headlines appeared in February 2011 across the country. This is a follow up of shocking deaths of 12 pregnant women in two government hospitals in Jodhpur reported to be due to administration of contaminated intravenous fluids. The preliminary report has identified multidrug-resistant bacteria as a cause of deaths and the intravenous fluids are suspected to be the source of the infecting bacteria. The intravenous fluid samples taken from the hospitals have tested positive for bacterial endotoxins.

This tragedy is not an isolated incident. There are innumerable instances of such incidents of administering the contaminated intravenous fluids. Here is one more infamous incident that happened in 1995.  The Indus Hospital at Shimla filed complaint about the fungus in various batches of intravenous fluids on 30th November 1995 to the Drugs Controller, Himachal Pradesh. Then hospital authorities subsequently complained about the presence of fungus in five bottles of dextrose injection. The similar fungus contaminations in intravenous fluids were reported in Delhi’s RML hospital in 1997. These incidents led to the investigation of quality related issues of contaminated intravenous fluids by the National Human Rights Commission (NHRC). The Expert Committee constituted by the NHRC submitted its reported entitled “Large Volume Parenteral Towards Zero Defects” in January 1999. The committee recommended continuing education and training  to the hospital staff including pharmacists, nurses, doctors in the visual inspection of particulate matter before administering intravenous fluids to the patients, in addition to setting up of policy and procedure for procurement from multisource with proper storage and distribution. Unfortunately even after 12 years of such recommendations, the tragedy continues to occur following administration of contaminated intravenous fluids.

Here is another incident reported in UK. In the early 1970s, a UK manufacturer produced an infusion fluid which caused the death of five patients due to heavy contamination with bacteria. Before distributing the fluid, the company had tested the samples for tests for sterility and the samples drawn for testing complied with the requirements. The subsequent investigations revealed that the fault was with the steriliser. The bottles at the bottom were not sterilized and the samples drawn for testing by the manufacturer were from upper part, giving false impression that all the bottles were sterile.

Between summer 1970 and March 1971, many US hospitals experienced outbreaks of intravenous associated septicaemia which was ultimately traced back to intrinsic contamination of infusion products. In a just happened incident, the supplier pharmacy has recalled all total parenteral nutrition products causing outbreak of Serratia marcescens bacteraemia in six Alabama Hospitals, USA.
All these incidents confirm one thing that the unfortunate incident may occur anywhere but they are preventable. The present series of two articles makes an attempt to present the overview of the intravenous fluids, their utilities, and the precautions required during their use to prevent these untoward incidents.

Beginning of intravenous medication
The beginning of intravenous medication started in 1662 by Johann Daniel Major of Kiel but was later abandoned for a period because the patients so treated developed thrombosis and embolism. Now the intravenous administration of drugs is a routine method of medication in hospitals so as the use of intravenous fluids.  Today intravenous therapy is a routine live saving practice treating patients with critical illness. The intravenous fluids are also known as large volume parenterals. They are slowly administered by intravenous infusions to replenish body fluids or electrolyte or to provide nutrition.

The fluid and electrolyte therapy is useful for correcting existing imbalances, maintaining the additional requirements and compensating additional losses. When the patient has undergone a heavy loss of water and electrolytes in cases like severe diarrhoea or vomiting, correcting the imbalance is a primary measure to save life. Acute diarrhoea continues to be one of the main reasons of mortality under age five. Patients with Crohn’s disease, AIDS, burns, or trauma do need replacement therapy. The normal body requirement of water for adults is about 25-40 ml/kg of body weight, or an average of about 2 litres per square meter of body surface area. Like dose of medicines, the water requirement is also more closely relate to the body surface area than body weight. The two–thirds of the body weight in normal individual are that of water. The water loss in the form of urine and faeces; and through the skin and respiration must be compensated. Intake of approximately 2 litres of water per day is sufficient to keep normal homeostasis in absence of exaggerated fluid gains or losses. The water alone cannot be administered intravenously as the osmotic haemolysis of red blood cells is likely; it is always administered as a solution with dextrose or isotonic solution with electrolytes such as sodium. The intravenous fluid therapy may cause water overload especially in elderly patients, patients with cardiovascular or renal disorders. In such situation, the monitoring of blood pressure is desirable.

Sodium is the principal extracellular cation and is vital to maintain normal extracellular fluids. The renal regulation of sodium excretion and conservation is excellent. Approximately 80% of the sodium (so also other potassium and other electrolytes) presented to the kidney from the plasma is reabsorbed. The low sodium concentration in the body may occur due to excessive sweating, use of certain diuretics, or diarrhoea. The excessive loss of sodium may cause fatigue, muscle weakness, and convulsion. On the other hand, the excess concentration may occur, if a person does not drink enough water especially in hot weather or when kidney function is impaired.  The symptoms of excess sodium include dry and sticky mucous membrane, flushed skin, elevated body temperature, lack of tears, thirst and high blood pressure. Potassium is also a intracellular cation and is important for normal cardiac and skeletal muscle function.  The potassium loss occurs through excessive perspiration, repeated enemas, trauma such severe burns, uncontrolled diabetes, disease of intestinal tract, surgical operations and use of thiazide and loop diuretics. The potassium loss may be reflected as weak pulse, faint heart sounds, falling blood pressure, and general weakness. Severe loss of potassium may lead to death. On the other hand excess potassium may cause diarrhoea, irritability, muscle cramps and pain. The excess of potassium may also happen by kidney failure or due to excessive consumption of potassium rich foods. Care is required while using the potassium preparations as they are required to be added to large volume intravenous fluids before infusion. The monitoring of serum potassium level is necessary. Chloride is the principal anion of extracellular fluid and is important for muscle contraction, balancing the fluid levels inside and outside the cells, and maintaining the acid-base balance of extracellular fluid. An adequate supply of chloride is necessary to maintain bicarbonate balance. Both sodium and potassium are commonly replaced as chloride salts, any excess of which is easily excreted by the kidneys.

The patients undergoing maintenance or replacement therapy are usually associated with caloric deficiency. These patients are given intravenous dextrose as 5% solution to reduce the caloric deficit.  The dextrose performs double function: source of calories and makes the solution compatible for intravenous administration. 5% dextrose solution is isotonic with blood. The caloric deficiency causes breakdown of body’s protein to meet the general requirements of dextrose.

Authors are with Division of Pharmacy Practice, Department of Pharmacy, Annamalai University, Annamalai Nagar, TN 608 002)