Pinchas Halpern

Mechanics of respiratory muscles

Lung ventilation is a mechanical process in which the respiratory muscles are acting in concert to remove air in and out of the lungs. Any alteration in the performance of the respiratory muscle may reduce the effectiveness of ventilation. Thus, early diagnosis of their weakness is vital for treatment and rehabilitation. Different techniques, which are based on different measurement protocols, can be utilized for evaluation of respiratory muscle strength. Respiratory muscle strength can be assessed using pressure measurement either from the mouth or from the nostril during quasi-static breathing. However, it estimates only global performance of respiratory muscles. Techniques that are based on electromyography measurements during muscle contraction (EMG) enable the differentiation between the different respiratory muscles. Along with the above clinical and physiological techniques for assessment of respiratory muscle strength and endurance, mechanical and mathematical models of the chest wall were developed in the last few decades for analysis of chest wall movements and the contribution of its components to respiration. In this review, the different methods and the models utilized for evaluation of respiratory muscles function will be discussed.

Middle cerebral artery flow velocity decreases and electroencephalogram (EEG) changes occur as acute hypercapnia reverses

ObjectiveTo define the changes in middle cerebral artery flow velocity (Vmca) and the electroencephalogram (EEG) during rapid reduction in arterial carbon dioxide (PCO2) from acute hypercapnia.DesignHuman volunteer study.SettingUniversity-affiliated hospital experimental laboratory.ParticipantsNine healthy volunteers aged 25–35xa0years.InterventionsSubjects rebreathed exhaled gas from a bag pre-filled with 5% carbon dioxide (CO2) in oxygen, up to an end-tidal CO2 of 10% or to the limit of discomfort, when they were disconnected.Measurements and resultsMiddle cerebral artery blood flow velocity was continuously measured by transcranial Doppler ultrasound, quantitative EEG was recorded and hemodynamics were monitored non-invasively. Vmca closely correlated with end-tidal CO2 changes (r=0.65, p<0.001). When rebreathing ceased, there was a rapid decline in end-tidal CO2 and in Vmca to baseline within 42±14xa0s, followed by a rapid further decline in both variables to below baseline. End-tidal CO2 reached a nadir of 4.4±1.1% at 146±79xa0s, with Vmca decreasing to 37±10xa0cm/s at 104±65xa0s (a 40% reduction and 31% below basal values). Electroencephalogram alpha activity significantly decreased and delta activity increased during hypercapnia. During subsequent hypocapnia, delta activity decreased back to baseline, while alpha activity increased, but remained below baseline.ConclusionsThese findings demonstrate the rapid changes occurring in cerebral blood flow during rapid declines in arterial CO2 and the consequent potential for producing brain ischemia and hemodynamic alterations if inadvertent hyperventilation occurs following institution of mechanical ventilation for acute hypercapnia.

The use of flumazenil in the treatment of 34 intoxicated patients

The efficacy and safety of the newly available benzodiazepine (BDZ) antagonist flumazenil (Ro 15-1788, Anexate) was prospectively evaluated in the treatment of 34 intoxicated patients. Twenty-three patients had attempted suicide with various drugs, and 11 suffered iatrogenic BDZ overdose. Following 0.2 mg i.v. flumazenil (Flu) injection, 22 patients intoxicated mainly with BDZ (11 iatrogenic and 11 intentional) regained full consciousness within two minutes, enabling even extubation of two. Eight patients required repeated boluses or continuous infusion of Flu to maintain alertness. Five patients with mixed drug intoxication awakened only briefly and relapsed into unconsciousness. In spite of Flu doses of up to 20 mg, no effect on consciousness was observed in 7 patients, intoxicated mainly with non-BDZ drugs. No significant side effects were noted attributable to Flu which has proved to be a safe and effective drug. It may be employed to achieve complete reversal of pure BDZ overdose, or for unmasking the relative action of BDZ in mixed drug overdose. The danger of complications from drug overdose may thus be lessened, obviating the need for invasive interventions such as mechanical ventilation and invasive hemodynamic monitoring, at the same time decreasing risk and expense.

CARDIORESPIRATORY EFFECTS OF ANTAGONISM OF DIAZEPAM SEDATION WITH FLUMAZENIL IN PATIENTS WITH CARDIAC DISEASE

&NA; The specific benzodiazepine antagonist flumazenil is currently under intense study. Despite much clinical experience, no detailed invasive hemodynamic studies of its use in cardiac patients have been published. In the present study, hemodynamic and respiratory variables were measured in 10 cardiac patients undergoing catheterization of the right and left sides of the heart, before and after sedation with intravenous diazepam, and after reversal of sedation with flumazenil. A sleep dose of diazepam (12.2 ± 5.1 mg, mean ± SD) caused only slight decreases in mean arterial pressure (103 ± 12 to 98 ± 14 mm Hg; P < 0.05), pulmonary capillary wedge pressure (13.2 ± 6.3 to 11.7 ± 6.6 mm Hg; P < 0.05), and left ventricular end‐diastolic pressure (20.8 ± 7.5 to 17.3 ± 10.0 mm Hg; P < 0.05), with no significant changes in respiratory gas homeostasis. Intravenous flumazenil (0.22 ± 0.07 mg) resulted in spontaneous awakening and return to full orientation, yet caused no significant alteration in either hemodynamic or respiratory variables measured. Reversal of diazepam‐induced sedation by flumazenil in cardiac patients appears safe and effective.

Ro 5-4864 has a negative inotropic effect on human atrial muscle strips that is not antagonized by PK 11195

The effects of Ro 5-4864, a peripheral benzodiazepine receptor agonist (9 x 10(-6) M and 9 x 10(-5) M) and of PK 11195, a peripheral benzodiazepine receptor antagonist (3 x 10(-6) M and 3 x 10(-5) M), alone or together, on contraction parameters of human atrial muscle strips were studied. Atrial muscle strips were obtained from patients undergoing cardiac surgery. The strips were suspended in Krebs-Henseleit solution at 36.8 +/- 0.2 degrees C, connected to an isometric force transducer and then stimulated at 15 V above threshold and paced at 1.5 Hz. Ro 5-4864 at its higher concentration, alone or mixed with PK 11195 at both concentrations, depressed the contraction amplitude to 80% of the control value (P < 0.05). In conclusion, Ro 5-4864 had a small but significant depressant effect on the contraction amplitude of human atrial strips. Surprisingly, this effect was not reversed by the peripheral benzodiazepine receptor antagonist PK 11195.

Midazolam infusion and the benzodiazepine antagonist flumazenil for sedation of intensive care patients

ICU patients often require sedation. Midazolam (M), a new imidazobenzodiazepine, features rapid onset and rapid elimination time. Flumazenil (Ro 15-1788) is a new benzodiazepine antagonist. We studied the efficacy and safety of M by continuous infusion in 28 ICU patients: 16 post major surgery, and 12 medical patients, aged 20-77 years. M was administered as a loading dose of 0.05-0.15 mg/kg per min followed by continuous infusion of 0.05-0.1 mg/kg per h titrated to maintain patients asleep but arousable. M was administered for up to 14 days in doses of 1-15 mg/h and cumulative doses of up to 1915 mg. No untoward effects were noted except for slight decreases in blood pressure following the loading dose. ACTH challenge tests performed before and 24 h or more following the start of M showed no depression of adrenal responsivity. All patients meeting weaning criteria were weaned off mechanical ventilation while still on M. In 13 patients extubation was performed immediately after M was stopped, and flumazenil (0.38 +/- 0.27 mg, i.v.) given until full awakening. Patients remained awake yet calm. Vital signs remained stable after flumazenil. Midazolam by continuous infusion appears to be a safe and effective mode of sedation in ICU patients. Flumazenil may increase the flexibility and safety of this mode of sedation.

Early use of naloxone in shock — A clinical trial

Naloxone hydrochloride (N) 0.4-1.2 mg i.v. was administered during 10 episodes of shock (8 septic and 2 cardiogenic) in 9 adult patients. Shock was defined as systolic blood pressure (SBP) less than or equal to 90 mmHg and urine output less than 0.5 ml/h and signs and symptoms of hypoperfusion lasting for greater than or equal to 30 min, despite fluid loading to a CVP 5 cmH2O above baseline. N was given as early as 30 min after onset of shock and resulted in an increase of SBP from a mean of 75 +/- 10 to a mean of 130 +/- 25 mmHg maximum (P less than 0.01). Within 10-60 min urine output increased from 16 +/- 12 to 122 +/- 56 ml/h, heart rate, CVP and arterial blood gas tensions remained unchanged. No side effects were observed. Naloxone, even in small doses, may improve hemodynamic parameters in human shock, provided it is administered very early.

Sepsis, septic shock, and fatal exertional heat stroke

Exertional heat stroke (EHS) is a clinical syndrome of hyperthermia, encephalopathy, and multiorgan dysfunction that can be irreversible and fatal. While prompt recognition and immediate, aggressive total body cooling can prevent progression of the clinical syndrome, even a short delay can exacerbate the effects of hyperthermia-induced changes. EHS is linked to an inflammatory response that is akin to the systemic inflammatory response syndrome (SIRS). However because EHS is not a common problem in most hospital intensive care units and is not in the usual list of SIRS causes, it may be overlooked easily. Furthermore normalizing the body temperature of patients with EHS, especially when hyperthermia recognition and total body cooling are delayed, may not prevent SIRS and its clinical consequences. This narrative review focuses on the inflammatory response behind the pathway leading to EHS-associated organ pathology and recommends a new insight to possible clinical interventions beyond whole body cooling.

Ophthalmologists, suicide bombings and getting it right in the emergency department

BackgroundThe number and extent of worldwide suicide attacks has risen sharply in recent years. The objectives of this retrospective study are: to determine the prevalence and outcome of the victims who sustained ocular injury, to describe the activities of ophthalmologists in the setting of an emergency department (ED) receiving mass casualties of a suicide bombing attack and to illustrate some of the treatment obstacles that they encountered and the protocol.MethodsA single-centre, retrospective, interventional case series.ParticipantsParticipants were the victims of 13 suicide bombing attacks (2000–2004), treated at a level I trauma center of an Israeli tertiary care, municipal medical center.Main outcome measuresThe study includes a description of the ophthalmologist’s role in the setting of mass evacuation to emergency facilities, prevalence and outcome of patients managed according to the recommended guidelines, and reemphasis of logistic and therapeutic guidelines for management of ocular injuries.ResultsThe trauma center database yielded information on a total of 352 casualties from 13 suicide bombing attacks, including 17 surviving patients with any ocular/periocular trauma resulting from suicide bombing attacks. Six eyes required and underwent urgent primary closure of laceration for primary repair of open globe, one unsalvageable eye underwent primary enucleation, and two eyes underwent exploration of subconjunctival hemorrhage. Four eyes required additional surgical intervention, which was performed within 7 days (large intravitreal foreign bodies were extracted from three eyes whose final visual acuity was poor, and an intra-lenticular foreign body was extracted from the fourth eye whose final visual acuity was 6/12). The remaining eight patients received medical treatment as indicated and were continued to be followed up.DiscussionOcular trauma management under conditions of mass injuries requires special utilization of manpower and resources. Guidelines for efficacious patient management, description of the ophthalmologist’s role, and the experience of one emergency facility are presented.

In vitro model of intravenous fluid administration: analysis of vein resistance to rapid fluid delivery

Rapid fluid administration is the cornerstone of successful trauma resuscitation of patients in a state of shock. Intravenous (IV) fluid delivery is a physical intrusion into a vein which results in a complex interaction between the rigid catheter and the compliant vein. We present an experimental model of IV infusion into a vein-like compliant tube that (a) demonstrated the interdependence between fluid administration and blood flow in a compliant tube and (b) allowed investigation of the contribution of the central venous system (between the infusion site and the heart) to the total resistance to infusion flow rate. The results show that in cases with very high resistance in the central venous system a significant increase of infusion flow rate cannot be achieved just by increasing the infusion pressure. Similarly, in cases of small veins when only small catheters can be used, infusate flow rate may be increased only by using two independent infusion ports. In cases with increased tissue pressure due to edema, gravity-driven infusion may not produce sufficient perfusion of the vascular compartments. It was also shown that the vein valves do not always close, and that peripheral blood flow may continue together with the infusate fluid (e.g., when there is a small downstream resistance and infusion with a small catheter).