A Neuroanatomical Construct for the Amnesic Effects of Propofol

Background: This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task.

Methods: Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline.

Results: Nonoverlapping memory effects were evident: low (n = 4; propofol concentration 523 +/- 138 ng/ml; 44 +/- 13% decrement from baseline memory) and high (n = 7; 829 +/- 246 ng/ml; 87 +/- 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z = 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases.     

Memory: a guide for anaesthetists

Episodic memory is the most 'human' of all memory systems, is integrally related to the hippocampus, and not only permits memories of the past in rich detail, but also allows projection of thoughts into the future. However, episodic memory is very sensitive to anaesthetic drugs and cannot be formed during adequate general anaesthesia. Ablation of episodic memory during consciousness is due to forgetting of memories, rather than inhibition of memory formation. There is a fine balance between being conscious with recollection and conscious with no recollection. A more detailed understanding of episodic memory in relation to other memory systems, as well as the relationship of the hippocampus to episodic memory function is provided. A synthesis of diverse knowledge is undertaken to identify potential mechanisms of amnesic drug effect, which will, of course, require further research to delineate.     

Effects of dantrolene and verapamil on atrioventricular conduction and cardiovascular performance in dogs

The effects of intravenous dantrolene sodium, alone and in combination with verapamil, upon atrioventricular conduction, cardiovascular function, and neuromuscular function were studied in chloralose-urethane anesthetized dogs. Hemodynamic variables (systemic arterial, central venous, and pulmonary arterial pressures and cardiac output) and His-bundle electrograms were monitored, and measurements were made during atrial pacing at 175 beats/min, as well as at the spontaneous heart rate. In one part of the study animals received dantrolene sodium incrementally at 30-min intervals to cumulative doses of 1, 2.5, 5, and 10 mg/kg. Subsequently, verapamil was administered incrementally at 30-min intervals to cumulative doses of 0.1, 0.2, 0.4, and 0.6 mg/kg. In the second part of the study, dogs received identical dosage sequences, but verapamil preceded dantrolene administration. Dantrolene caused no significant depression of atrioventricular conduction or cardiac performance but did increase systemic vascular resistance at doses above 2.5 mg/kg. Verapamil alone (greater than or equal to 0.2 mg/kg) or with dantrolene (greater than or equal to 0.1 mg/kg) increased the atrial-His-bundle conduction interval. In the presence of verapamil, dantrolene (greater than or equal to 2.5 mg/kg) decreased cardiac index and increased pulmonary artery occlusion pressure. Although 0.6 mg/kg verapamil depressed cardiac index and increased pulmonary artery occlusion pressure, this effect was observed at 0.4 mg/kg after prior treatment with dantrolene. Verapamil did not augment the dose-dependent twitch depression observed with dantrolene. Dantrolene alone had no apparent effect on atrioventricular conduction and caused little enhancement of the effects of verapamil. However, each drug appeared to enhance the myocardial depressant effects of the other.     

Sedation and pain management for the critically ill

Critically ill cancer patients may present special problems. Often these patients are terminally ill and mortality in a critical care unit devoted to cancer patients is higher than in other units. Sedation becomes paramount in the treatment of these patients. Some techniques may be inappropriate, such as epidural narcotics in a patient who is thrombocytopenic from chemotherapy. Drug pharmacokinetics are ill defined in these patients who often have liver and renal failure either resulting from tumor or chemotherapy. As the number of available drugs increases, interactions among these drugs become more important. Very little investigations has been done with the drugs we used everyday in the ICU. One should carefully titrate medication to effect--not rely on standard dosage regimens that have been primarily determined in relatively healthy patients. Combinations of techniques are being used, such as PCA with epidural narcotic administration with short acting, lipid soluble narcotics. Nerve blocks, primarily intercostal for chest trauma, were used in the past, but the requirement for frequent reinjection has made them less desirable. Recently thoracic paravertebral block has been used successfully for 9 to 10 hour pain relief with chest trauma. With this armamentarium of techniques and drugs, the critical care physicians should be able to go a long way to relieve pain and suffering of patients in the ICU.     

Information loss over time defines the memory defect of propofol: a comparative response with thiopental and dexmedetomidine

BACKGROUND: Sedative-hypnotic drugs impair memory, but details regarding the nature of this effect are unknown. The influences of propofol, thiopental, and dexmedetomidine on the performance of a task that isolates specific components of episodic memory function were measured. METHODS: Working (1 intervening item, 6 s) and long-term memory (10 intervening items, 33 s) were tested using auditory words in a continuous recognition task before and during drug administration. Eighty-three volunteer participants were randomly assigned to receive a constant target concentration of drug or placebo, producing sedative effects from imperceptible to unresponsiveness. Responsive participants were categorized as high or low performers, using a median split of long-term memory performance during drug administration. Recognition of words at the end of the study day was assessed. RESULTS: High performers had acquisition of material into long-term memory when drug was present at the same level as placebo. Retention of this material at 225 min was significantly less for propofol (39 +/- 23% loss of material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low performers was evident in multiple measures. Memory for words presented before drug was no different from that associated with placebo for all groups. CONCLUSIONS: Lack of retention of material acquired into long-term memory during propofol administration, associated with minimal sedation, seems to define drug-induced amnesia. Sedation seems to impair the acquisition or encoding of material into long-term memory. Therefore, the putative targets of drug-induced amnesia by propofol are processes associated with retention of material in long-term memory.     

Information Loss over Time Defines the Memory Defect of Propofol: A Comparative Response with Thiopental and Dexmedetomidine

Background: Sedative-hypnotic drugs impair memory, but details regarding the nature of this effect are unknown. The influences of propofol, thiopental, and dexmedetomidine on the performance of a task that isolates specific components of episodic memory function were measured.

Methods: Working (1 intervening item, 6 s) and long-term memory (10 intervening items, 33 s) were tested using auditory words in a continuous recognition task before and during drug administration. Eighty-three volunteer participants were randomly assigned to receive a constant target concentration of drug or placebo, producing sedative effects from imperceptible to unresponsiveness. Responsive participants were categorized as high or low performers, using a median split of long-term memory performance during drug administration. Recognition of words at the end of the study day was assessed.

Results: High performers had acquisition of material into long-term memory when drug was present at the same level as placebo. Retention of this material at 225 min was significantly less for propofol (39 +/- 23% loss of material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low performers was evident in multiple measures. Memory for words presented before drug was no different from that associated with placebo for all groups.     

Bone Tumors Occurring in the Soft Tissues: A Review of the Clinical,Imaging, and Histopathologic Findings

Although rare in everyday practice, malignancies that classically arise from bone or cartilage have been reported to arise de novo in various soft tissues in the body, resulting in a diagnostic challenge for the clinician, radiologist, and pathologist.Differential diagnoses of bone tumors often depend on anatomic location of the lesion. For example, the classic location of osteosarcoma is in the metaphysis of long bones about the knee. Histologically osteosarcoma is characterized by tumor cells that directly produce osteoid, bone, or cartilaginous matrix. In extraskeletal osteosarcoma, the clinical and radiologic picture is very different from a conventional osteosarcoma. They occur in older patients, present as a soft tissue mass often coincidentally following trauma and have a worse prognosis. The imaging characteristics are often nonspecific with mineralized elements in a well-defined soft tissue mass. The mineralized elements may or may not be visible. Magnetic Resonance sequences demonstrate a well circumscribed soft tissue mass with hemorrhagic and enhancing solid components. The pathologic features of extraskeletal osteosarcoma on a microscopic scale are identical to that of skeletal lesions. Likewise, conventional chondrosarcomas present in older patients with a growing, painful soft tissue prominence most commonly involving the long tubular bones. In extraskeletal chondrosarcoma however, the presentation is in somewhat younger patients with a painful soft tissue prominence typically in the head (meninges), neck, or upper leg. The pathologic features are most often that of a myxoid chondrosarcoma which is characterized by strands of small cells over a myxoid matrix. Imaging features include chondroid matrix, heterogenous contrast enhancement, and amorphous internal calcification on Computed Tomography. On Magnetic Resonance sequences the matrix has a low signal on all sequences, and variable inhomogeneity depending on grade of the lesion. Other extraskeletal bone tumors include Ewing's sarcoma and osteoid osteoma amongst other lesions.Although these malignancies may be rare clinical entities, they often exhibit characteristic clinical, imaging, and histopathological findings although differing in treatment and prognosis. Knowledge of these and other common mimicking lesions will help guide the clinician and radiologist to make an accurate diagnosis.     

Intravenous narcotics in the ICU

In summary, there are now available very potent narcotics, with small side effect liability. Critical care physicians should be experts in administration of intravenous narcotics and should understand the concepts behind different methods of administration. Much more patient satisfaction and safety can be obtained if as much attention is paid to how a drug is administered as to its pharmacologic actions. Intravenous administration allows rapid and almost complete control of desired effect. Intravenous access is universally available in the ICU population, and we should take every advantage of it.