Author Correction: Waist circumference and the risk of lumbar and femur fractures: a nationwide population-based cohort study.

Correction to: European Review for Medical and Pharmacological Sciences 2021; 25 (3): 1198-1205-DOI: 10.26355/eurrev_202102_24822-PMID: 33629289, published online 15 February, 2021. After publication, the authors requested to correct Table I and some minor errors in the text. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/24822.

Waist circumference and the risk of lumbar and femur fractures: a nationwide population-based cohort study.

Although obesity is known to have an influence on fracture, the relationship between lumbar and femur fractures and weight or waist circumference is controversial. We investigated the incidence of fracture with regards to waist circumference using the customised database of the Korean National Health Insurance Service (NHIS). Among 8,922,940 adults who participated at least twice in the NHIS National Health Check-up Program in South Korea between 2009 and 2011, 1,556,751 subjects (780,074 men and 776,677 women) were extracted. Over a mean follow-up of 6.5 years, multivariate-adjusted logistic regression analysis demonstrated that higher waist circumference was associated with an increased risk of femur fractures in both males and females. Moreover, the incidence of lumbar fractures was also positively associated with an increased waist circumference in males and females. An increased waist circumference showed a positive linear relationship with the risk of lumbar and femur fractures in both males and females.

Alfentanil infusions in patients requiring intensive care.

Alfentanil is a short acting opioid that has an established place in anaesthesia. Its predictable pharmacokinetics and pharmacodynamics, particularly its rapid termination of effect and haemodynamic stability, have led to its use by continuous intravenous infusion both during anaesthesia and more recently in critically ill patients. Fine control of a potent analgesic that has respiratory depressant and antitussive properties would be particularly advantageous in this group, offering patients an improvement in comfort without increasing the risk of oversedation. Pharmacokinetic studies of alfentanil have demonstrated wide interindividual variations. This may be due to a wide variety of factors including age, obesity, hepatic dysfunction, changes in regional haemodynamics, sex, and alterations in plasma protein binding ability and concentration. The importance of pharmacogenetic differences and tolerance to alfentanil remains to be elucidated. Renal disease does not appear to significantly alter the pharmacokinetics of this agent, which may make it particularly useful in this situation. Since alfentanil does not depress conscious level or produce anxiolysis, additional agents such as a benzodiazepine will be necessary to provide adequate sedation. The difficulties in accurately predicting the response of an individual critically ill patient necessitate careful and continuous dose titration of alfentanil according to the clinical response.

The altered pharmacokinetics and pharmacodynamics of drugs commonly used in critically ill patients.

The critically ill patient occupies an increasing amount of time and bed space in modern hospital practice, and also commands increasing expenditure. Drug therapy in these patients has, in the past, been based on data derived from healthy volunteers, fit anaesthetised patients undergoing minor operative procedures, or patients with single organ failure. Alterations in pharmacokinetics and pharmacodynamics have not been studied in depth in critically ill patients who often have multisystem failure. This paper reviews the currently available information on drugs in common usage in these patients. The studies that have been performed have usually shown delayed drug clearance, altered volumes of distribution and prolonged elimination half-lives. The sedative and analgesic drugs, in particular, have shown marked accumulation which may confuse the clinical picture, and prolonged periods of assisted ventilation may be required until the drugs are eliminated.

The use of sedative agents in critically ill patients.

The main aim of sedation in the critically ill patient is to provide relief from anxiety and pain. The current, ideal level of sedation should leave a patient who is lightly asleep but easily roused. No single regimen is suitable for all patients. The level of sedation should be monitored, and the choice of agent, the dose and the route of administration adjusted appropriately. Midazolam is often used to provide sleep and anxiolysis. Alternatives include propofol and isoflurane. Propofol is easily titrated to achieve the desired level of sedation, and its effects rapidly end when the infusion is stopped. Isoflurane also appears promising, but special equipment is needed for its administration. Morphine is the standard analgesic agent. The principal metabolites, morphine-6-glucuronide, is also a potent opioid agonist and may accumulate in renal failure. Of the newer analgesic agents, alfentanil is an ideal agent for infusion, and may be the agent of choice in renal failure. Neuromuscular blocking agents are indicated only in specific circumstances, and used only once it is known patients are asleep and pain free. The actions of these agents are unpredictable in the critically ill patient. Alterations in drug effect and elimination may occur, especially in the patient with hepatic and renal failure. This may also apply to active metabolites of the parent drug. When planning sedation regimens, specific patient needs and staffing levels must be remembered. Attention to the environment is also important. Midazolam and morphine given by intermittent bolus or by infusion are the mainstay of most regimens. Propofol is ideal for short periods of care on the ICU, and during weaning when longer acting agents are being eliminated.

Characterization of the enzyme responsible for the metabolism of sumatriptan in human liver.

Studies have been undertaken to investigate the enzymes responsible for the metabolism of [14C]sumatriptan in man. Oxidative deamination of sumatriptan to form the indole acetic acid derivative is the only phase 1 pathway evident in man and both cytochrome P450 (P450) and monoamine oxidase (MAO) are capable of catalysing this type of reaction. The metabolism of [14C]sumatriptan was therefore investigated in vitro in a preparation derived from human liver, which was shown, by the use of the probe substrates [14C]testosterone (P450), [3H]5HT (MAO-A) and [14C]benzylamine (MAO-B) to be a rich source of both enzyme systems. Incubation with clorgyline and deprenyl, probe inhibitors of MAO-A and MAO-B, respectively, showed that [14C]sumatriptan was metabolized by MAO-A; there was no evidence of P450 involvement in its metabolism. The data in this study therefore indicate that the enzyme MAO-A is the major enzyme responsible for the metabolism of sumatriptan in human liver.

Care of the multiple organ donor.

Successful organ transplantation offers patients with end stage organ failure the chance of a normal life. The recognition of brain death allowed the use of beating heart donors and this has enabled multiple organ procurement from a single donor. Suitable patients with severe brain injury resulting in brain death, who may be potential organ donors, are to be found on both neurosurgical and general intensive care units. The pathophysiological results of brain death are similar, irrespective of the underlying cause. Severe brain injury may result in the loss of temperature regulation, and the development of diabetes insipidus and cardiovascular instability. The management of brain injury before death often results in abnormalities of fluid balance, due to fluid restriction and diuretic therapy. Other problems such as acute endocrine failure and the impact of their correction on ultimate organ function remains to be elucidated. Good donor maintenance in the intensive care unit and operating theatre is essential if optimal function of the transplanted organ is to occur.

Dopexamine hydrochloride, a novel drug with renal vasodilator properties: two case studies.

Two patients who received an infusion of dopexamine hydrochloride are presented. The dopexamine infusion was associated with a useful increase in urine output. The mechanisms for these effects are discussed and the renovascular dilatation associated with dopexamine highlighted.

A nomogram for rapid calculation of metabolic requirements on intubated patients.

There is a need for estimating the calorific requirements of patients undergoing or about to undergo total parenteral nutrition (TPN) other than by complicated direct calorimetry or by guesswork. We describe a simple, cheap, indirect calorimetric method for determining energy requirements from the measurement of mixed expired carbon dioxide tension (PECO2) in patients who are intubated, and in whom the breathing circuit characteristics allow collection of pure expired gas. This can be achieved by collection of expired gas from ventilators where an on-demand fresh gas flow rather than a continuous flow occurs during spontaneous or intermittent positive pressure ventilation, such as with the Siemens Servo 900C.

The physiological effects of vasopressin when used to control intra-abdominal bleeding.

Vasopressin was used in ten critically ill patients with massive intra-abdominal bleeding unresponsive to conventional therapy. Vasopressin controlled bleeding in four patients, three of whom had continued to bleed following laparotomy for haemostasis; in two other patients, bleeding was reduced. All the patients were intensively monitored throughout the period of the vasopressin treatment; this enabled other physiological effects of vasopressin to be documented and reported. Mean arterial pressure and central venous pressure increased following the administration of vasopressin and there was a decrease in heart rate. Core body temperature rose significantly. Although all the patients had impaired renal function before receiving vasopressin, five had a prompt diuresis following its administration. Eight patients died but only three of intra-abdominal bleeding; two patients survived to leave hospital. Four patients had post-mortem evidence of ischaemia in the heart, liver and gastrointestinal tract; vasopressin may have contributed to the development of this. Vasopressin may have a place in the management of patients with life-threatening intra-abdominal haemorrhage but its use should be confined to those patients in whom conventional therapy has failed.

Portable lung ventilators: the potential risk from bacterial colonisation.

Seven portable lung ventilators were investigated to assess the risk of bacterial colonization of the ventilator valve. One valve was deliberately contaminated with Serratia marcescens and the survival of organisms within the valve studied. Periods of colonization by Acinetobacter were found in all the hospital ventilators studied but none of those from the ambulance service. The potential risk to the patient from this organism is discussed and the importance of adequate storage and regular cleaning of the ventilator valve emphasised. Since humidification of the patients inspired gas during transfer is desirable, the use of a combined heat and moisture exchanger and microbiological filter would appear advisable.

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions.

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.

Brain stem death and organ donation.

Organs for donation are in short supply in the United Kingdom, resulting in allegations that relatives of potential donors are not being asked for consent. Legislation on "required request" has been proposed to overcome this. The incidence, causes, complications, and patterns of organ donation in brain stem dead patients in one referral centre were studied over 12 months. Data were collected on all patients fulfilling criteria for brain stem death or considered suitable for donating organs after circulatory arrest. Forty two patients fulfilled the criteria for brain stem death, and in 10 further patients circulatory arrest occurred before formal testing was finished. The major causes of brain stem death were head injury (28) and intracranial haemorrhage (17). Consent to organ donation was obtained for 24 potential donors, and organs were donated by 23 of them. Twenty nine patients did not donate organs. The commonest reasons for failure to donate were medical unsuitability (13) and the coroner not releasing the body (eight). Consent was not sought in three cases, and the relatives refused consent in the remaining five. This study suggests that required request will not considerably increase the supply of donor organs.

Desflurane and the sensitivity of upper airway reflexes.

Sixty consecutive patients who were given an anesthetic, not needing tracheal intubation, received desflurane as part of the anesthetic technique to assess the incidence of upper airway irritation. A variety of induction agents and artificial airways were used. The incidence of upper airway irritation was recorded. Eight patients coughed at induction. Five of these were related to insertion of a laryngeal mask and probably represent light anesthesia. One was unrelated to instrumentation, another caused by a partially obstructed airway and the final one occurred in a child with an upper respiratory tract infection. Six episodes of coughing and hiccoughs occurred after the end of anesthesia. Four were related to removal of an airway. Five episodes of coughing occurred in the ten smokers, confirming the importance of this as a risk factor. Six patients who coughed were given no premedication or were anesthetized before it could take effect. Coughing occurs during general anesthesia, but it is caused by many factors. In adults, using desflurane it does not appear to be a significant risk factor.

Morphine elimination and hepatic blood flow--a study in patients with portal hypertension.

To investigate the influence of changes in portal venous blood flow on the clearance of morphine, the elimination of a single intravenous dose of morphine sulphate was studied in twelve patients with periportal fibrosis undergoing distal splenorenal shunt for portal hypertension. All patients had almost normal preoperative liver function. Six patients (Group A) received morphine after induction of anesthesia but before surgery; a further six patients (Group B) received morphine after completion of the splenorenal shunt and removal of all vascular clamps. Blood was sampled for 24 hours after morphine administration and analysed for plasma morphine concentration using high performance liquid chromatography. The maximum concentration of morphine was significantly greater in those patients in Group B who received morphine after the shunt (P < .002). Clearance of morphine during the operation was also significantly reduced in these patients compared with the initial clearance (before release of the clamps) in Group A (P < .004). As a consequence of these changes the AUC was greater in this group (P < 0.004). However, there were no differences with the elimination rates after surgery had finished. The results suggest that in individuals with normal liver function, the clearance of morphine is dependent on hepatic blood flow.

Humidification of inspired gases during mechanical ventilation.

Humidification of inspired gas is mandatory for all mechanically ventilated patients to prevent secretion retention, tracheal tube blockage and adverse changes occurring to the respiratory tract epithelium. However, the debate over "ideal" humidification continues. Several devices are available that include active and passive heat and moisture exchangers and hot water humidifiers Each have their advantages and disadvantages in mechanically ventilated patients. This review explores each device in turn and defines their role in clinical practice.